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  • Genomics  (47)
  • bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
  • Oxford University Press  (60)
  • Cambridge University Press  (7)
  • Bristol University Press  (5)
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  • 1
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    Oxford University Press
    Publication Date: 2021-02-10
    Description: A democratic regime is assumed to implement freedom and equality as the two critical and most important values. The question we intend to address here is: how and why has the actual implementation of freedom and equality been changing in the 1990–2020 period? Researching this topic, we cannot ignore the impact of the Great Recession since 2008. Thus, in this comparative research, we analyse France, Germany, Italy, Poland, Spain, and the United Kingdom to detect the changes. As expected, the six largest European democracies have been differently affected by the crisis, as they also had different background factors. We address an additional question: what is the impact of the European Union on the two democratic values? Accordingly, we analyse economic inequality, social inequality, and ethnic inequality with the related changing trends and explanations. We also detect and analyse the trend of freedoms, and especially personal dignity, civil rights, and political rights. Thus, the relative decline of equalities and freedoms in the six countries emerge in the different complex facets. We also explore the demand for equalities and freedoms by citizens and the political commitments of party leaders. The other issues we address include how and why, respectively, equalities and freedoms are affected by domestic aspects and the role of external factors, especially the European Union. By connecting equalities and freedoms and drawing the lines of entire research, we show how there are three different paths in the future of democracy: balanced democracy, protest democracy, and unaccountable democracy.
    Keywords: democracy ; equality ; freedom ; great recession ; inter-institutional accountability ; rule of law ; responsiveness ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPB Comparative politics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::1 Geographical Qualifiers::1Q Other geographical groupings, oceans & seas::1QF Political, socio-economic & strategic groupings::1QFE EU (European Union)
    Language: English
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  • 2
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    Cambridge University Press
    Publication Date: 2022-08-09
    Description: Why has there been uneven success in reducing air pollution even in the same locality over time? This book offers an innovative theorization of how local political incentives can systematically affect bureaucratic regulation and empirically examines the control of different air pollutants in China and – to a lesser extent – in Mexico.?
    Keywords: political theory ; environmental law and engineering ; China studies ; air pollution studies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCN Environmental economics ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPA Political science & theory
    Language: English
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  • 3
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    Oxford University Press
    Publication Date: 2022-05-13
    Description: The concepts of cultural diversity and cultural identity are at the forefront of the political debate in many western societies. In Europe, the discussion is stimulated by the political pressures associated with immigration flows, which are increasing in many European countries. The imperatives that current immigration trends impose on European democracies bring to light a number of issues that need to be addressed. What are the patterns and dynamics of cultural integration? How do they differ across immigrants of different ethnic groups and religious faiths? How do they differ across host societies? What are the implications and consequences for market outcomes and public policy? Which kind of institutional contexts are more or less likely to accommodate the cultural integration of immigrants? All these questions are crucial for policy makers and await answers. This book aims to provide a stepping stone to the debate. Taking an economic perspective, this edited book presents a current, comparative picture of the process of cultural integration of immigrants across Europe. It documents the main economic debates on the causes and consequences of cultural integration of immigrants, and provides detailed descriptions of the cultural and economic integration process in seven main European countries, including France, Germany, Italy, Spain, Sweden, Switzerland, and the United Kingdom. It also compares the European context with the integration of immigrants in the United States.
    Keywords: immigration ; european models of integration ; economic integration ; integration of immigrants ; cultural integration ; Eastern Europe ; Ethnic group ; Germany ; Second-generation immigrants in the United States ; Switzerland ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFF Social issues & processes::JFFN Migration, immigration & emigration ; bic Book Industry Communication::J Society & social sciences::JH Sociology & anthropology::JHB Sociology::JHBD Population & demography ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 4
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    Cambridge University Press
    Publication Date: 2022-08-09
    Description: International economic institutions economise climate change, treating it as an economic rather than environmental issue. This book explores how three such institutions - G20, IMF, OECD - have addressed climate finance and fossil fuel subsidies, and the consequences of the economisation of climate change. Also available as Open Access.
    Keywords: climate change ; environmental policy ; environmental economics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCN Environmental economics ; bic Book Industry Communication::R Earth sciences, geography, environment, planning::RN The environment::RNP Pollution & threats to the environment::RNPG Climate change ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies::KNB Energy industries & utilities::KNBP Petroleum & oil industries ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 5
    Publication Date: 2022-08-09
    Description: This book is an analytical examination of financing and public service delivery challenges in a decentralized framework. In addition, it provides critical insights into the effectiveness of public expenditure, through benefit incidence analysis of education and healthcare services in India.
    Keywords: economics ; policy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPP Public administration ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 6
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    Cambridge University Press
    Publication Date: 2023-06-06
    Description: Jacqueline Best argues that the changes in International Monetary Fund, World Bank and donor policies in the 1990s, towards what some have called the 'Post-Washington Consensus,' were driven by an erosion of expert authority and an increasing preoccupation with policy failure. Failures such as the Asian financial crisis and the decades of despair in sub-Saharan Africa led these institutions to develop governance strategies designed to avoid failure: fostering country ownership, developing global standards, managing risk and vulnerability and measuring results. In contrast to the structural adjustment era when policymakers were confident that they had all the answers, the author argues that we are now in an era of provisional governance, in which key actors are aware of the possibility of failure even as they seek to inoculate themselves against it. This book considers the implications of this shift, asking if it is a positive change and whether it is sustainable. This title was made Open Access by libraries from around the world through Knowledge Unlatched.
    Keywords: nongovernmental organisations ; economic assistance ; politics ; development banks ; economic development - finance ; corporate governance ; international devleopment policy ; Conditionality ; Good governance ; Structural adjustment ; World Bank ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 7
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    Oxford University Press
    Publication Date: 2021-02-10
    Description: This book analyses the role of public action in solving the problem of hunger in the modern world. The study is divided into four parts. The first, making extensive use of the concepts of entitlements and capabilities explores the interaction of nutritional, economic, social, and political elements and their influence on hunger and deprivation. The problem of famine prevention is the main focus of the second part, with special attention given to Africa and India. The third part is devoted to the issue of fighting chronic undernourishment and the lessons to be learnt from the policies of China, India, and some other countries. The last part draws together the main themes and concerns of the earlier chapters, and provides an integrated view of the role of public action in eliminating hunger. The study suggests that there is indeed some space for public action in solving the problem of hunger and deprivation. In the case of famine prevention, social security could provide early warning systems and employment provision plans. To fight endemic deprivation, the authors suggest, among other things, that basic health care, elementary education, and food programmes should be looked at.
    Keywords: capability ; chronic undernourishment ; deprivation ; entitlements ; famine ; hunger ; public action ; social security ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCR Welfare economics
    Language: English
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  • 8
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    Oxford University Press
    Publication Date: 2023-08-17
    Description: Why do certain parts of the state in Africa work so effectively despite operating in difficult governance contexts? How do 'pockets of bureaucratic effectiveness' emerge and become sustained over time? And what does this tell us about the prospects for state-building and development in Africa? Repeated economic and social crises have demanded that development thinkers and policy actors have had to engage with the critical role that states play in delivering development. Pockets of Effectiveness and the Politics of State-building and Development in Africa shows that politics is the driving factor that shapes how well state agencies perform their roles. It deploys a new conceptual framework – the power domains approach – to explore the shifting fortunes of key state agencies in five countries – Ghana, Kenya, Rwanda, Uganda, and Zambia – over the past three decades. Our original research reveals when, how and why political rulers decide to build effective state agencies and enable them to deliver certain forms of economic development – often through forming strategic coalitions with senior bureaucrats and with international support – and also when this support falters and gives way to a politics of survival. Comparative analysis identifies two potential trajectories towards state-building in Africa, each shaped by different configurations of social and political power. The book critiques the role that international development agencies have played in (mis)shaping the state in Africa and suggests a new strategic agenda for building the state capacities required to deliver sustained development at the current juncture. The book closes with critical commentaries from two leading scholars in the field, to help place our work in context and establish the next steps for research and strategy in this increasingly important area of development theory and practice.
    Keywords: Development studies, Political economy, Public administration, and African Studies ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GT Interdisciplinary studies::GTF Development studies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPP Public administration ; bic Book Industry Communication::1 Geographical Qualifiers::1H Africa
    Language: English
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  • 9
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    Cambridge University Press
    Publication Date: 2022-08-09
    Description: This element explores early and more recent contributions of the policy feedback literature to clarify the meaning of this concept and its contribution to both political science and policy studies. This element also discusses the practical implications of policy feedback research through a discussion of its potential impact on policy design.
    Keywords: Public policy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPP Public administration ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPH Political structure & processes
    Language: English
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  • 10
    Publication Date: 2022-09-06
    Description: Few concepts have captured the imagination of the conflict and development communities in recent years as powerfully as the idea of a ‘political settlement’. At its most ambitious, ‘political settlements analysis’ (PSA) promises to explain why conflicts occur and states collapse, the conditions for their successful rehabilitation, different developmental pathways from peace, and how to better fit development policy to country context. Yet despite the meteoric rise of the term and its tremendous promise, not all is well in the world of PSA. Rival definitions of the concept abound; there are disagreements about its scope and the way it should be used; a growing schism between conflict specialists and economists; basic concepts are ambiguous; and little progress has been made on measurement. This book consequently has three main aims. The first is to argue for a revised definition of a political settlement, capable of unifying its diverse strands. The second is to put the concept on a more solid theoretical and scientific footing, providing a method for measuring and categorizing political settlements, using both qualitative case studies and a large-n statistical analysis to illustrate its potential. And the third is to examine the implications of the findings for mainstream social science analysis and for policymakers.
    Keywords: Government Policy, Provision and Effects of Welfare Programmes, Economic Development, Development Planning and Policy, Rent-Seeking, Lobbying, Elections, Legislatures, and Voting Behavior, Bureaucracy, Administrative Processes in Public Organizations, Corruption, Conflict, Conflict Resolution, Alliances, Revolutions, Positive Analysis of Policy Formulation and Implementation, Political Economy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCS Economic systems & structures
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  • 11
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    Oxford University Press
    Publication Date: 2021-02-10
    Description: Why do governments in some developing countries implement international standards, while others do not? Focusing on the politics of bank regulation, this book develops a new framework to explain regulatory interdependence between countries in the core and the periphery of the global financial system. Drawing on in-depth analysis of eleven countries across Africa, Asia, and Latin America, it shows how financial globalization generates strong reputational and competitive incentives for developing countries to converge on international standards. Regulatory interdependence is generated by relations between regulators, politicians, and banks within developing countries, and international actors including investors, peer regulators, and international financial institutions. We explain why it is that some configurations of domestic politics and forms of integration into global finance generate convergence with international standards, while other configurations lead to divergence. This book contributes to our understanding of the ways in which governments and firms in the core of global finance powerfully shape regulatory politics in the periphery, and the ways in which peripheral governments and firms manoeuvre within the constraints and opportunities created by financial globalization
    Keywords: Africa ; Asia ; Latin America ; financial globalization ; regulatory interdependence ; international banking standards ; Basel I ; Basel II ; Basel III ; transnational policy networks ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPA Political science & theory ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPB Comparative politics ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GT Interdisciplinary studies::GTF Development studies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies
    Language: English
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  • 12
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    Oxford University Press
    Publication Date: 2022-04-28
    Description: It is now widely accepted that politics plays a significant role in shaping the possibilities for inclusive development. However, the specific ways in which this happens across different types and forms of development, and in different contexts, remains poorly understood. This collection provides the state of the art review regarding what is currently known about the politics of inclusive development. Leading academics offer systematic reviews of how politics shapes development across multiple dimensions, including through growth, natural resource governance, poverty reduction, service delivery, social protection, justice systems, the empowerment of marginalized groups, and the role of both traditional and non-traditional donors. The book not only provides a comprehensive update but also a groundbreaking range of new directions for thinking and acting around these issues. The book’s originality thus derives not only from the wide scope of its case-study material, but also from the new conceptual approaches it offers for thinking about the politics of inclusive development, and the innovative and practical suggestions for donors, policymakers, and practitioners that flow from this.
    Keywords: citizenship ; transnational ; politics ; recognition ; inclusive development ; political settlement ; accumulation ; China ; Economic growth ; Ethnic group ; Welfare ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCB Macroeconomics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 13
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    Bristol University Press
    Publication Date: 2022-08-25
    Description: The digital PDF of the Introduction, Chapter 3, Chapter 8 and the Afterword of this title are available Open Access under CC-BY-NC-ND licence. The word ‘precarity’ is widely used when discussing work and employment, social conditions and lived experiences, and social classes. There is not, however, a consensus on the precise meaning of the term or how it should best be used to explore social changes. Bringing together an international group of thinkers from a diverse range of fields, this book offers a distinctive and critical perspective approach to an important topic.
    Keywords: Contingency; Critical; Employment; Insecurity; Platform economy; Social class; Social conditions; Temporary work ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management
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  • 14
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    Oxford University Press
    Publication Date: 2021-02-10
    Description: This book presents the findings of original field research into the design, practice, and varied outcomes of industrial policy in three sectors in Ethiopia, covering export-oriented and import-substitution industries. The three sectors are cement, leather and leather products, and floriculture. Given that there is a single industrial strategy, why do its outcomes vary across sectors? To what extent is this a function of the specific market and political economy features of each sector? The book examines industrial structures and associated global value chains to demonstrate the challenges faced by African firms in international markets. Part of the book’s relevance is the light it throws on the whole question of industrial policy in low-income countries, the subject of renewed discussion among development economists and organizations in recent years. The findings are also discussed in the light of the history of, and the history of thought about, industrialization. Insights for researchers and policymakers emerge from the analysis of failures and successes in the three industrial sectors. The book also challenges prevailing wisdom on how much and what kind of state intervention is required to support transformational industrial policy in Africa. Among other things, the book highlights the significance for policy design of maximizing linkage effects, backward and forward, from particular industries and activities.
    Keywords: development economics & emerging economies ; economics of industrial organisation ; political economy ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCD Economics of industrial organisation ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 15
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    Bristol University Press
    Publication Date: 2022-08-25
    Description: The digital PDF of the Introduction of this title are available Open Access under CC-BY-NC-ND licence. The word ‘precarity’ is widely used when discussing work and employment, social conditions and lived experiences, and social classes. There is not, however, a consensus on the precise meaning of the term or how it should best be used to explore social changes. Bringing together an international group of thinkers from a diverse range of fields, this book offers a distinctive and critical perspective approach to an important topic.
    Keywords: Contingency; Critical; Employment; Insecurity; Platform economy; Social class; Social conditions; Temporary work ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management
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  • 16
    Publication Date: 2022-08-25
    Description: The digital PDF of Chapter 3 is available Open Access under CC-BY-NC-ND licence. The word ‘precarity’ is widely used when discussing work and employment, social conditions and lived experiences, and social classes. There is not, however, a consensus on the precise meaning of the term or how it should best be used to explore social changes. Bringing together an international group of thinkers from a diverse range of fields, this book offers a distinctive and critical perspective approach to an important topic.
    Keywords: Contingency; Critical; Employment; Insecurity; Platform economy; Social class; Social conditions; Temporary work ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management
    Language: English
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  • 17
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    Bristol University Press
    Publication Date: 2022-08-25
    Description: The digital PDF of Chapter 8 of this title is available Open Access under CC-BY-NC-ND licence. The word ‘precarity’ is widely used when discussing work and employment, social conditions and lived experiences, and social classes. There is not, however, a consensus on the precise meaning of the term or how it should best be used to explore social changes. Bringing together an international group of thinkers from a diverse range of fields, this book offers a distinctive and critical perspective approach to an important topic.
    Keywords: Contingency; Critical; Employment; Insecurity; Platform economy; Social class; Social conditions; Temporary work ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management
    Language: English
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  • 18
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    Oxford University Press
    Publication Date: 2024-03-29
    Description: The Global Financial Crisis (GFC) is the most serious economic crisis since the Great Depression. Many books have explored its causes, but this book systematically explores its consequences. The focus is primarily on the policy and political consequences of the GFC. This book asks how governments responded to the challenge and what the political consequences of the combination of the GFC itself and policy responses to it have been. Based on workshops held in the United States and the United Kingdom, it brings together leading academics to consider the divergent ways in which particular countries have responded in different ways to the crisis, including China, France, the United Kingdom, and the United States. Part of what is happening is a structural shift in economic power from east to west, but China has its fragilities while Germany offers an example of a largely successful Western model. The book also assesses attempts to develop global economic governance and to reform financial regulation and looks critically at the role of credit rating agencies. Unlike earlier crises, no new paradigm has emerged to challenge existing ways of thinking, meaning that neoliberalism has emerged relatively unscathed. The crisis has lacked a coherent and innovative intellectual response and has been characterized by remarkable policy stability.
    Keywords: neoliberalism ; structural change ; financial regulation ; global financial crisis ; China ; International Monetary Fund ; Non-commercial activity ; United States ; bic Book Industry Communication::J Society & social sciences::JP Politics & government ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management ; thema EDItEUR::J Society and Social Sciences::JP Politics and government ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCP Political economy ; thema EDItEUR::K Economics, Finance, Business and Management::KJ Business and Management
    Language: English
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  • 19
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    Oxford University Press
    Publication Date: 2022-09-06
    Description: This book provides a systematic analysis of the political processes shaping the distribution of social transfers in six countries in sub-Saharan Africa and South Asia. In doing so, the book addresses a notable gap in recent research on social protection concerning the politics of implementation. While considerable attention has been devoted to debating the merits of different policy designs and the political factors shaping the adoption and diffusion of different policy models, ultimately the ability of any social transfer programme to deliver on its promises is dependent on the effective implementation and distribution of social transfers in line with intended objectives. The chapters in this book examine international and sub-national variation in programme implementation in Bangladesh, Ethiopia, Ghana, Kenya, Nepal, and Rwanda, drawing on a common analytical framework that highlights the importance of state capacity and reach, rooted in histories of state formation, and contemporary political competition in shaping the distribution of social transfers. Comparative analysis of the case studies supports the view that variation in the capacity and reach of the state within countries is a centrally important factor shaping the effectiveness and impartiality of distribution. Yet state capacity alone is insufficient. Rather, political competition and power relations shape how this capacity is actually deployed in practice. As such, the book underscores the inherently political nature of implementation and questions common technocratic efforts to improve implementation by de-politicizing the social protection policy process.
    Keywords: social protection, social transfer, policy implementation, political economy, power relations, state capacity, Africa, South Asia ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFF Social issues & processes ; bic Book Industry Communication::G Reference, information & interdisciplinary subjects::GT Interdisciplinary studies::GTF Development studies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies
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  • 20
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    Oxford University Press
    Publication Date: 2021-02-10
    Description: "As their Millennium Development Goals, world leaders have pledged by 2015 to halve the number of people living in extreme poverty and hunger, to achieve universal primary education, to reduce child mortality, to halt the spread of HIV/AIDS, and to halve the number of people without safe drinking water. Achieving these goals requires a large increase in the flow of financial resources to developing countries – double the present development assistance from abroad. In examining innovative ways to secure these resources, this book, which is part of the UNU–WIDER Studies in Development Economics series, sets out a framework for the economic analysis of different sources of funding and applying the tools of modern public economics to identify the key issues. It examines the role of new sources of overseas aid, considers the fiscal architecture and the lessons that can be learned from federal fiscal systems, asks how far increased transfers impose a burden on donors, and investigates how far the raising of resources can be separated from their use. In turn, the book examines global environmental taxes (such as a carbon tax), the taxation of currency transactions (the Tobin tax), a development‐focused allocation of Special Drawing Rights by the International Monetary Fund (IMF), the UK Government proposal for an International Finance Facility, increased private donations for development purposes, a global lottery (or premium bond), and increased remittances by emigrants. In each case, it considers the feasibility of the proposal and the resources that it can realistically raise, and offers new perspectives and insights into these new and controversial proposals. "
    Keywords: child mortality reduction ; development economics ; allocation of Special Drawing Rights by IMF ; development assistance ; development finance ; economic analysis ; environmental taxes ; federal fiscal systems ; funding ; global lottery ; global premium bond ; HIV/AIDS spread prevention ; hunger reduction ; International Finance Facility ; Millennium Development Goals ; poverty alleviation ; private donations ; remittances by emigrants ; safe drinking water ; sources of funding ; sources of overseas aid ; Special Drawing Rights ; taxation of currency transactions ; Tobin tax ; universal primary education ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCL International economics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KF Finance & accounting::KFF Finance::KFFD Public finance::KFFD1 Taxation
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  • 21
    Publication Date: 2022-08-09
    Description: Ageing societies can be healthy and productive- if they get the politics right. This book argues that the population ageing crisis can be solved through policies that reduce inequalities between and within generations. It then explores the political coalitions needed to support policymaking that avoids pitting generations against each other.
    Keywords: economics of ageing ; politics of ageing ; healthy ageing ; ageing crisis ; health policy ; health systems ; healthcare management ; public policy ; public finance ; intergenerational justice ; welfare state ; pensions ; pension policy ; public health ; bic Book Industry Communication::K Economics, finance, business & management ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 22
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    Cambridge University Press
    Publication Date: 2022-08-09
    Description: This Element goes beyond traditional texts which focus on public policy as an activity of states to outline how global policy making has driven many global and regional transformations over the past quarter-century. This title is also available as Open Access on Cambridge Core.
    Keywords: public policy ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPP Public administration ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPA Political science & theory ; bic Book Industry Communication::J Society & social sciences::JP Politics & government::JPS International relations::JPSN International institutions ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
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  • 23
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    Oxford University Press
    Publication Date: 2024-03-29
    Description: "International financial crises have plagued the world in recent decades, including the Latin American debt crisis of the 1980s, the East Asian crisis of the late twentieth century, and the global financial crisis of 2007-09. One of the basic problems faced during these crises is the lack of adequate preventive mechanisms, as well as insufficient instruments to finance countries in crisis and to overcome their over-indebtedness. Resetting the International Monetary (Non)System provides an analysis of the global monetary system and the necessary reforms that it should undergo to play an active role in the twenty-first century and proposes a comprehensive yet evolutionary reform of the system. Criticising the ad hoc framework- a ""(non)system""- that has evolved following the breakdown of the Bretton Woods arrangement in the early 1970's, Resetting the International Monetary (Non)System places a special focus on the asymmetries that emerging and developing countries face, analysing the controversial management of crises by the International Monetary Fund and proposing a consistent set of reform proposals to design a better system of international monetary cooperation. Policy orientated and structured to deal in a sequential way with the issues involved, it suggests provision of international liquidity through a system that mixes the multicurrency arrangement with a more active use of the IMF's Special Drawing Rights; stronger mechanisms of macroeconomic policy cooperation, including greater cooperation in exchange rate management and freedom to manage capital flows; additional automatic balance-of-payments financing facilities and the complementary use of swap and regional arrangements; a multilateral sovereign debt workout mechanism; and major reforms of the system's governance."
    Keywords: economics ; monetary economics ; Ghana ; Gross domestic product ; Liberia ; Malaysia ; Thailand ; Uganda ; bic Book Industry Communication::J Society & social sciences::JP Politics & government ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCG Economic growth ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; thema EDItEUR::J Society and Social Sciences::JP Politics and government ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCG Economic growth ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCM Development economics and emerging economies ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCP Political economy
    Language: English
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  • 24
    facet.materialart.
    Unknown
    Bristol University Press
    Publication Date: 2022-08-25
    Description: The digital PDF of the Afterword of this title are available Open Access under CC-BY-NC-ND licence. The word ‘precarity’ is widely used when discussing work and employment, social conditions and lived experiences, and social classes. There is not, however, a consensus on the precise meaning of the term or how it should best be used to explore social changes. Bringing together an international group of thinkers from a diverse range of fields, this book offers a distinctive and critical perspective approach to an important topic.
    Keywords: Contingency; Critical; Employment; Insecurity; Platform economy; Social class; Social conditions; Temporary work ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management
    Language: English
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  • 25
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    Unknown
    Oxford University Press
    Publication Date: 2021-02-10
    Description: Authored by eminent scholars, the volume aims to generate interest and debate among policymakers, practitioners, and researchers on the complexity of learning and catch-up, particularly for twenty-first century late-late developers. The volume explores technological learning at the firm level, policy learning by the state, and the cumulative and multifaceted nature of the learning process, which encompasses learning by doing, by experiment, emulation, innovation, and leapfrogging. Why is catch-up rare? And why have some nations succeeded while others failed? What are the prospects for successful learning and catch-up in the twenty-first century? These are pertinent questions that require further research and in-depth analysis. The World Bank estimates that out of the 101 middle-income economies in 1960, only thirteen became high income by 2008. This volume examines how nations learn by reviewing key structural and contingent factors that contribute to dynamic learning and catch-up. Rejecting both the one-size-fits-all approach and the agnosticism that all nations are unique and different, the volume uses historical as well as firm-level, industry-level, and country-level evidence and experiences to identify the sources and drivers of successful learning and catch-up and the lessons for late-latecomer countries. Building on the latecomer-advantage perspective, the volume shows that what is critical for dynamic learning and catch-up is not learning per se but the intensity of learning, robust industrial policies, and the pace and direction of learning. Equally important are the passion to learn, long-term strategic vision, and understanding the context in which successful learning occurs.
    Keywords: catch-up ; technological learning ; industrial policy ; latecomers ; intensity of learning ; policy learning ; emualation ; innovation ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCG Economic growth ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCM Development economics & emerging economies ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy ; bic Book Industry Communication::K Economics, finance, business & management::KN Industry & industrial studies
    Language: English
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  • 26
    Publication Date: 2015-09-19
    Description: Clonal populations accumulate mutations over time, resulting in different haplotypes. Deep sequencing of such a population in principle provides information to reconstruct these haplotypes and the frequency at which the haplotypes occur. However, this reconstruction is technically not trivial, especially not in clonal systems with a relatively low mutation frequency. The low number of segregating sites in those systems adds ambiguity to the haplotype phasing and thus obviates the reconstruction of genome-wide haplotypes based on sequence overlap information. Therefore, we present EVORhA, a haplotype reconstruction method that complements phasing information in the non-empty read overlap with the frequency estimations of inferred local haplotypes. As was shown with simulated data, as soon as read lengths and/or mutation rates become restrictive for state-of-the-art methods, the use of this additional frequency information allows EVORhA to still reliably reconstruct genome-wide haplotypes. On real data, we show the applicability of the method in reconstructing the population composition of evolved bacterial populations and in decomposing mixed bacterial infections from clinical samples.
    Keywords: Genomics
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  • 27
    Publication Date: 2015-08-29
    Description: Data on biological mechanisms of aging are mostly obtained from cross-sectional study designs. An inherent disadvantage of this design is that inter-individual differences can mask small but biologically significant age-dependent changes. A serially sampled design (same individual at different time points) would overcome this problem but is often limited by the relatively small numbers of available paired samples and the statistics being used. To overcome these limitations, we have developed a new vector-based approach, termed three-component analysis, which incorporates temporal distance, signal intensity and variance into one single score for gene ranking and is combined with gene set enrichment analysis. We tested our method on a unique age-based sample set of human skin fibroblasts and combined genome-wide transcription, DNA methylation and histone methylation (H3K4me3 and H3K27me3) data. Importantly, our method can now for the first time demonstrate a clear age-dependent decrease in expression of genes coding for proteins involved in translation and ribosome function. Using analogies with data from lower organisms, we propose a model where age-dependent down-regulation of protein translation-related components contributes to extend human lifespan.
    Keywords: Genomics
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  • 28
    Publication Date: 2015-05-29
    Description: A major challenge in the field of shotgun metagenomics is the accurate identification of organisms present within a microbial community, based on classification of short sequence reads. Though existing microbial community profiling methods have attempted to rapidly classify the millions of reads output from modern sequencers, the combination of incomplete databases, similarity among otherwise divergent genomes, errors and biases in sequencing technologies, and the large volumes of sequencing data required for metagenome sequencing has led to unacceptably high false discovery rates (FDR). Here, we present the application of a novel, gene-independent and signature-based metagenomic taxonomic profiling method with significantly and consistently smaller FDR than any other available method. Our algorithm circumvents false positives using a series of non-redundant signature databases and examines G enomic O rigins T hrough T axonomic CHA llenge (GOTTCHA). GOTTCHA was tested and validated on 20 synthetic and mock datasets ranging in community composition and complexity, was applied successfully to data generated from spiked environmental and clinical samples, and robustly demonstrates superior performance compared with other available tools.
    Keywords: Genomics
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  • 29
    Publication Date: 2016-07-09
    Description: Chromosome-long haplotyping of human genomes is important to identify genetic variants with differing gene expression, in human evolution studies, clinical diagnosis, and other biological and medical fields. Although several methods have realized haplotyping based on sequencing technologies or population statistics, accuracy and cost are factors that prohibit their wide use. Borrowing ideas from group testing theories, we proposed a clone-based haplotyping method by overlapping pool sequencing. The clones from a single individual were pooled combinatorially and then sequenced. According to the distinct pooling pattern for each clone in the overlapping pool sequencing, alleles for the recovered variants could be assigned to their original clones precisely. Subsequently, the clone sequences could be reconstructed by linking these alleles accordingly and assembling them into haplotypes with high accuracy. To verify the utility of our method, we constructed 130 110 clones in silico for the individual NA12878 and simulated the pooling and sequencing process. Ultimately, 99.9% of variants on chromosome 1 that were covered by clones from both parental chromosomes were recovered correctly, and 112 haplotype contigs were assembled with an N50 length of 3.4 Mb and no switch errors. A comparison with current clone-based haplotyping methods indicated our method was more accurate.
    Keywords: Genomics
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  • 30
    Publication Date: 2016-07-28
    Description: Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these ‘repressed transcripts’ have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies.
    Keywords: Genomics
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  • 31
    Publication Date: 2013-06-08
    Description: DNA methylation is a mechanism for long-term transcriptional regulation and is required for normal cellular differentiation. Failure to properly establish or maintain DNA methylation patterns leads to cell dysfunction and diseases such as cancer. Identifying DNA methylation signatures in complex tissues can be challenging owing to inaccurate cell enrichment methods and low DNA yields. We have developed a technique called laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) for the multiplexed interrogation of the DNA methylation status of cytosine–guanine dinucleotide islands and promoters. LCM-RRBS accurately and reproducibly profiles genome-wide methylation of DNA extracted from microdissected fresh frozen or formalin-fixed paraffin-embedded tissue samples. To demonstrate the utility of LCM-RRBS, we characterized changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Compared with adjacent normal tissue, the adrenocortical tumors showed reproducible gains and losses of DNA methylation at genes involved in cell differentiation and organ development. LCM-RRBS is a rapid, cost-effective, and sensitive technique for analyzing DNA methylation in heterogeneous tissues and will facilitate the investigation of DNA methylation in cancer and organ development.
    Keywords: Genomics
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  • 32
    Publication Date: 2014-12-17
    Description: The advent in high-throughput-sequencing (HTS) technologies has revolutionized conventional biodiversity research by enabling parallel capture of DNA sequences possessing species-level diagnosis. However, polymerase chain reaction (PCR)-based implementation is biased by the efficiency of primer binding across lineages of organisms. A PCR-free HTS approach will alleviate this artefact and significantly improve upon the multi-locus method utilizing full mitogenomes. Here we developed a novel multiplex sequencing and assembly pipeline allowing for simultaneous acquisition of full mitogenomes from pooled animals without DNA enrichment or amplification. By concatenating assemblies from three de novo assemblers, we obtained high-quality mitogenomes for all 49 pooled taxa, with 36 species 〉15 kb and the remaining 〉10 kb, including 20 complete mitogenomes and nearly all protein coding genes (99.6%). The assembly quality was carefully validated with Sanger sequences, reference genomes and conservativeness of protein coding genes across taxa. The new method was effective even for closely related taxa, e.g. three Drosophila spp., demonstrating its broad utility for biodiversity research and mito-phylogenomics. Finally, the in silico simulation showed that by recruiting multiple mito-loci, taxon detection was improved at a fixed sequencing depth. Combined, these results demonstrate the plausibility of a multi-locus mito-metagenomics approach as the next phase of the current single-locus metabarcoding method.
    Keywords: Genomics
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  • 33
    Publication Date: 2014-12-17
    Description: Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes or are studied in vitro . Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.
    Keywords: Genomics
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  • 34
    Publication Date: 2015-04-02
    Description: With read lengths of currently up to 2 x 300 bp, high throughput and low sequencing costs Illumina's MiSeq is becoming one of the most utilized sequencing platforms worldwide. The platform is manageable and affordable even for smaller labs. This enables quick turnaround on a broad range of applications such as targeted gene sequencing, metagenomics, small genome sequencing and clinical molecular diagnostics. However, Illumina error profiles are still poorly understood and programs are therefore not designed for the idiosyncrasies of Illumina data. A better knowledge of the error patterns is essential for sequence analysis and vital if we are to draw valid conclusions. Studying true genetic variation in a population sample is fundamental for understanding diseases, evolution and origin. We conducted a large study on the error patterns for the MiSeq based on 16S rRNA amplicon sequencing data. We tested state-of-the-art library preparation methods for amplicon sequencing and showed that the library preparation method and the choice of primers are the most significant sources of bias and cause distinct error patterns. Furthermore we tested the efficiency of various error correction strategies and identified quality trimming (Sickle) combined with error correction (BayesHammer) followed by read overlapping (PANDAseq) as the most successful approach, reducing substitution error rates on average by 93%.
    Keywords: Genomics
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  • 35
    Publication Date: 2015-04-02
    Description: RNA-seq is a sensitive and accurate technique to compare steady-state levels of RNA between different cellular states. However, as it does not provide an account of transcriptional activity per se , other technologies are needed to more precisely determine acute transcriptional responses. Here, we have developed an easy, sensitive and accurate novel computational method, iRNA-seq , for genome-wide assessment of transcriptional activity based on analysis of intron coverage from total RNA-seq data. Comparison of the results derived from iRNA-seq analyses with parallel results derived using current methods for genome-wide determination of transcriptional activity, i.e. global run-on (GRO)-seq and RNA polymerase II (RNAPII) ChIP-seq, demonstrate that iRNA-seq provides similar results in terms of number of regulated genes and their fold change. However, unlike the current methods that are all very labor-intensive and demanding in terms of sample material and technologies, iRNA-seq is cheap and easy and requires very little sample material. In conclusion, iRNA-seq offers an attractive novel alternative to current methods for determination of changes in transcriptional activity at a genome-wide level.
    Keywords: Genomics
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  • 36
    Publication Date: 2016-01-09
    Description: Identifying large-scale structural variation in cancer genomes continues to be a challenge to researchers. Current methods rely on genome alignments based on a reference that can be a poor fit to highly variant and complex tumor genomes. To address this challenge we developed a method that uses available breakpoint information to generate models of structural variations. We use these models as references to align previously unmapped and discordant reads from a genome. By using these models to align unmapped reads, we show that our method can help to identify large-scale variations that have been previously missed.
    Keywords: Genomics
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  • 37
    Publication Date: 2015-08-29
    Description: Any given human individual carries multiple genetic variants that disrupt protein-coding genes, through structural variation, as well as nucleotide variants and indels. Predicting the phenotypic consequences of a gene disruption remains a significant challenge. Current approaches employ information from a range of biological networks to predict which human genes are haploinsufficient (meaning two copies are required for normal function) or essential (meaning at least one copy is required for viability). Using recently available study gene sets, we show that these approaches are strongly biased towards providing accurate predictions for well-studied genes. By contrast, we derive a haploinsufficiency score from a combination of unbiased large-scale high-throughput datasets, including gene co-expression and genetic variation in over 6000 human exomes. Our approach provides a haploinsufficiency prediction for over twice as many genes currently unassociated with papers listed in Pubmed as three commonly-used approaches, and outperforms these approaches for predicting haploinsufficiency for less-studied genes. We also show that fine-tuning the predictor on a set of well-studied ‘gold standard’ haploinsufficient genes does not improve the prediction for less-studied genes. This new score can readily be used to prioritize gene disruptions resulting from any genetic variant, including copy number variants, indels and single-nucleotide variants.
    Keywords: Genomics
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  • 38
    Publication Date: 2015-07-12
    Description: Meta-analysis of gene expression has enabled numerous insights into biological systems, but current methods have several limitations. We developed a method to perform a meta-analysis using the elastic net, a powerful and versatile approach for classification and regression. To demonstrate the utility of our method, we conducted a meta-analysis of lung cancer gene expression based on publicly available data. Using 629 samples from five data sets, we trained a multinomial classifier to distinguish between four lung cancer subtypes. Our meta-analysis-derived classifier included 58 genes and achieved 91% accuracy on leave-one-study-out cross-validation and on three independent data sets. Our method makes meta-analysis of gene expression more systematic and expands the range of questions that a meta-analysis can be used to address. As the amount of publicly available gene expression data continues to grow, our method will be an effective tool to help distill these data into knowledge.
    Keywords: Genomics
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  • 39
    Publication Date: 2016-08-20
    Description: Advanced sequencing technologies have generated a plethora of data for many chromatin marks in multiple tissues and cell types, yet there is lack of a generalized tool for optimal utility of those data. A major challenge is to quantitatively model the epigenetic dynamics across both the genome and many cell types for understanding their impacts on differential gene regulation and disease. We introduce IDEAS, an i ntegrative and d iscriminative e pigenome a nnotation s ystem, for jointly characterizing epigenetic landscapes in many cell types and detecting differential regulatory regions. A key distinction between our method and existing state-of-the-art algorithms is that IDEAS integrates epigenomes of many cell types simultaneously in a way that preserves the position-dependent and cell type-specific information at fine scales, thereby greatly improving segmentation accuracy and producing comparable annotations across cell types.
    Keywords: Genomics
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  • 40
    Publication Date: 2016-09-03
    Description: A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 x 10 –4 insertions per genome per generation and the rate of IS homologous recombination is 4.5 x 10 –5 recombinations per genome per generation. These events are mostly contributed by the IS elements IS 1 , IS 2 , IS 5 and IS 186 . Spatial analysis of new insertions suggest that transposition is biased to proximal insertions, and the length spectrum of IS-caused deletions is largely explained by local hopping. For any of the ISs studied there is no region of the circular genome that is favored or disfavored for new insertions but there are notable hotspots for deletions. Some elements have preferences for non-coding sequence or for the beginning and end of coding regions, largely explained by target site motifs. Interestingly, transposition and deletion rates remain constant across the wild-type and 12 mutant E. coli lines, each deficient in a distinct DNA repair pathway. Finally, we characterized the target sites of four IS families, confirming previous results and characterizing a highly specific pattern at IS 186 target-sites, 5'-GGGG(N6/N7)CCCC-3'. We also detected 48 long deletions not involving IS elements.
    Keywords: Genomics
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  • 41
    Publication Date: 2015-04-21
    Description: Extensive and multi-dimensional data sets generated from recent cancer omics profiling projects have presented new challenges and opportunities for unraveling the complexity of cancer genome landscapes. In particular, distinguishing the unique complement of genes that drive tumorigenesis in each patient from a sea of passenger mutations is necessary for translating the full benefit of cancer genome sequencing into the clinic. We address this need by presenting a data integration framework (OncoIMPACT) to nominate patient-specific driver genes based on their phenotypic impact. Extensive in silico and in vitro validation helped establish OncoIMPACT's robustness, improved precision over competing approaches and verifiable patient and cell line specific predictions (2/2 and 6/7 true positives and negatives, respectively). In particular, we computationally predicted and experimentally validated the gene TRIM24 as a putative novel amplified driver in a melanoma patient. Applying OncoIMPACT to more than 1000 tumor samples, we generated patient-specific driver gene lists in five different cancer types to identify modes of synergistic action. We also provide the first demonstration that computationally derived driver mutation signatures can be overall superior to single gene and gene expression based signatures in enabling patient stratification and prognostication. Source code and executables for OncoIMPACT are freely available from http://sourceforge.net/projects/oncoimpact .
    Keywords: Genomics
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  • 42
    Publication Date: 2015-05-20
    Description: Analysis of rewired upstream subnetworks impacting downstream differential gene expression aids the delineation of evolving molecular mechanisms. Cumulative statistics based on conventional differential correlation are limited for subnetwork rewiring analysis since rewiring is not necessarily equivalent to change in correlation coefficients. Here we present a computational method ChiNet to quantify subnetwork rewiring by statistical heterogeneity that enables detection of potential genotype changes causing altered transcription regulation in evolving organisms. Given a differentially expressed downstream gene set, ChiNet backtracks a rewired upstream subnetwork from a super-network including gene interactions known to occur under various molecular contexts. We benchmarked ChiNet for its high accuracy in distinguishing rewired artificial subnetworks, in silico yeast transcription-metabolic subnetworks, and rewired transcription subnetworks for Candida albicans versus Saccharomyces cerevisiae , against two differential-correlation based subnetwork rewiring approaches. Then, using transcriptome data from tolerant S. cerevisiae strain NRRL Y-50049 and a wild-type intolerant strain, ChiNet identified 44 metabolic pathways affected by rewired transcription subnetworks anchored to major adaptively activated transcription factor genes YAP1 , RPN4 , SFP1 and ROX1 , in response to toxic chemical challenges involved in lignocellulose-to-biofuels conversion. These findings support the use of ChiNet in rewiring analysis of subnetworks where differential interaction patterns resulting from divergent nonlinear dynamics abound.
    Keywords: Genomics
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  • 43
    Publication Date: 2015-06-24
    Description: Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein–RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein–rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a ‘proof of concept’ that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites.
    Keywords: Genomics
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  • 44
    Publication Date: 2015-02-18
    Description: The emergence of new sequencing technologies has facilitated the use of bacterial whole genome alignments for evolutionary studies and outbreak analyses. These datasets, of increasing size, often include examples of multiple different mechanisms of horizontal sequence transfer resulting in substantial alterations to prokaryotic chromosomes. The impact of these processes demands rapid and flexible approaches able to account for recombination when reconstructing isolates’ recent diversification. Gubbins is an iterative algorithm that uses spatial scanning statistics to identify loci containing elevated densities of base substitutions suggestive of horizontal sequence transfer while concurrently constructing a maximum likelihood phylogeny based on the putative point mutations outside these regions of high sequence diversity. Simulations demonstrate the algorithm generates highly accurate reconstructions under realistically parameterized models of bacterial evolution, and achieves convergence in only a few hours on alignments of hundreds of bacterial genome sequences. Gubbins is appropriate for reconstructing the recent evolutionary history of a variety of haploid genotype alignments, as it makes no assumptions about the underlying mechanism of recombination. The software is freely available for download at github.com/sanger-pathogens/Gubbins , implemented in Python and C and supported on Linux and Mac OS X.
    Keywords: Genomics
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  • 45
    Publication Date: 2015-02-18
    Description: Genomic structural variation (SV), a common hallmark of cancer, has important predictive and therapeutic implications. However, accurately detecting SV using high-throughput sequencing data remains challenging, especially for ‘targeted’ resequencing efforts. This is critically important in the clinical setting where targeted resequencing is frequently being applied to rapidly assess clinically actionable mutations in tumor biopsies in a cost-effective manner. We present BreaKmer, a novel approach that uses a ‘kmer’ strategy to assemble misaligned sequence reads for predicting insertions, deletions, inversions, tandem duplications and translocations at base-pair resolution in targeted resequencing data. Variants are predicted by realigning an assembled consensus sequence created from sequence reads that were abnormally aligned to the reference genome. Using targeted resequencing data from tumor specimens with orthogonally validated SV, non-tumor samples and whole-genome sequencing data, BreaKmer had a 97.4% overall sensitivity for known events and predicted 17 positively validated, novel variants. Relative to four publically available algorithms, BreaKmer detected SV with increased sensitivity and limited calls in non-tumor samples, key features for variant analysis of tumor specimens in both the clinical and research settings.
    Keywords: Genomics
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  • 46
    Publication Date: 2016-02-20
    Description: Genetic variants in or near miRNA genes can have profound effects on miRNA expression and targeting. As user-friendly software for the impact prediction of miRNA variants on a large scale is still lacking, we created a tool called miRVaS. miRVaS automates this prediction by annotating the location of the variant relative to functional regions within the miRNA hairpin (seed, mature, loop, hairpin arm, flanks) and by annotating all predicted structural changes within the miRNA due to the variant. In addition, the tool defines the most important region that is predicted to have structural changes and calculates a conservation score that is indicative of the reliability of the structure prediction. The output is presented in a tab-separated file, which enables fast screening, and in an html file, which allows visual comparison between wild-type and variant structures. All separate images are provided for downstream use. Finally, we tested two different approaches on a small test set of published functionally validated genetic variants for their capacity to predict the impact of variants on miRNA expression.
    Keywords: Genomics
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  • 47
    Publication Date: 2016-02-20
    Description: Analysis of RNA-seq data often detects numerous ‘non-co-linear’ (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts ( trans -spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method (‘NCLscan’), which utilized a stepwise alignment strategy to almost completely eliminate false calls (〉98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans -spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans -spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome.
    Keywords: Genomics
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  • 48
    Publication Date: 2015-12-02
    Description: Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.
    Keywords: Genomics
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  • 49
    Publication Date: 2013-12-07
    Description: Identity by descent (IBD) can be reliably detected for long shared DNA segments, which are found in related individuals. However, many studies contain cohorts of unrelated individuals that share only short IBD segments. New sequencing technologies facilitate identification of short IBD segments through rare variants, which convey more information on IBD than common variants. Current IBD detection methods, however, are not designed to use rare variants for the detection of short IBD segments. Short IBD segments reveal genetic structures at high resolution. Therefore, they can help to improve imputation and phasing, to increase genotyping accuracy for low-coverage sequencing and to increase the power of association studies. Since short IBD segments are further assumed to be old, they can shed light on the evolutionary history of humans. We propose HapFABIA, a computational method that applies biclustering to identify very short IBD segments characterized by rare variants. HapFABIA is designed to detect short IBD segments in genotype data that were obtained from next-generation sequencing, but can also be applied to DNA microarray data. Especially in next-generation sequencing data, HapFABIA exploits rare variants for IBD detection. HapFABIA significantly outperformed competing algorithms at detecting short IBD segments on artificial and simulated data with rare variants. HapFABIA identified 160 588 different short IBD segments characterized by rare variants with a median length of 23 kb (mean 24 kb) in data for chromosome 1 of the 1000 Genomes Project. These short IBD segments contain 752 000 single nucleotide variants (SNVs), which account for 39% of the rare variants and 23.5% of all variants. The vast majority—152 000 IBD segments—are shared by Africans, while only 19 000 and 11 000 are shared by Europeans and Asians, respectively. IBD segments that match the Denisova or the Neandertal genome are found significantly more often in Asians and Europeans but also, in some cases exclusively, in Africans. The lengths of IBD segments and their sharing between continental populations indicate that many short IBD segments from chromosome 1 existed before humans migrated out of Africa. Thus, rare variants that tag these short IBD segments predate human migration from Africa. The software package HapFABIA is available from Bioconductor. All data sets, result files and programs for data simulation, preprocessing and evaluation are supplied at http://www.bioinf.jku.at/research/short-IBD .
    Keywords: Genomics
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  • 50
    Publication Date: 2013-12-07
    Description: Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA–mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations≥30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression.
    Keywords: Genomics
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  • 51
    Publication Date: 2014-02-11
    Description: A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline ( http://canbind.princeton.edu ) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteins—specifically those known to be involved in molecular interactions—our approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer.
    Keywords: Genomics
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  • 52
    Publication Date: 2014-04-03
    Description: Genome duplication with hybridization, or allopolyploidization, occurs commonly in plants, and is considered to be a strong force for generating new species. However, genome-wide quantification of homeolog expression ratios was technically hindered because of the high homology between homeologous gene pairs. To quantify the homeolog expression ratio using RNA-seq obtained from polyploids, a new method named HomeoRoq was developed, in which the genomic origin of sequencing reads was estimated using mismatches between the read and each parental genome. To verify this method, we first assembled the two diploid parental genomes of Arabidopsis halleri subsp. gemmifera and Arabidopsis lyrata subsp. petraea ( Arabidopsis petraea subsp. umbrosa ), then generated a synthetic allotetraploid, mimicking the natural allopolyploid Arabidopsis kamchatica . The quantified ratios corresponded well to those obtained by Pyrosequencing. We found that the ratios of homeologs before and after cold stress treatment were highly correlated ( r = 0.870). This highlights the presence of nonstochastic polyploid gene regulation despite previous research identifying stochastic variation in expression. Moreover, our new statistical test incorporating overdispersion identified 226 homeologs (1.11% of 20 369 expressed homeologs) with significant ratio changes, many of which were related to stress responses. HomeoRoq would contribute to the study of the genes responsible for polyploid-specific environmental responses.
    Keywords: Genomics
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  • 53
    Publication Date: 2015-03-14
    Description: Methods to interpret personal genome sequences are increasingly required. Here, we report a novel framework (EvoTol) to identify disease-causing genes using patient sequence data from within protein coding-regions. EvoTol quantifies a gene's intolerance to mutation using evolutionary conservation of protein sequences and can incorporate tissue-specific gene expression data. We apply this framework to the analysis of whole-exome sequence data in epilepsy and congenital heart disease, and demonstrate EvoTol's ability to identify known disease-causing genes is unmatched by competing methods. Application of EvoTol to the human interactome revealed networks enriched for genes intolerant to protein sequence variation, informing novel polygenic contributions to human disease.
    Keywords: Genomics
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  • 54
    Publication Date: 2015-03-14
    Description: Detecting in vivo transcription factor (TF) binding is important for understanding gene regulatory circuitries. ChIP-seq is a powerful technique to empirically define TF binding in vivo . However, the multitude of distinct TFs makes genome-wide profiling for them all labor-intensive and costly. Algorithms for in silico prediction of TF binding have been developed, based mostly on histone modification or DNase I hypersensitivity data in conjunction with DNA motif and other genomic features. However, technical limitations of these methods prevent them from being applied broadly, especially in clinical settings. We conducted a comprehensive survey involving multiple cell lines, TFs, and methylation types and found that there are intimate relationships between TF binding and methylation level changes around the binding sites. Exploiting the connection between DNA methylation and TF binding, we proposed a novel supervised learning approach to predict TF–DNA interaction using data from base-resolution whole-genome methylation sequencing experiments. We devised beta-binomial models to characterize methylation data around TF binding sites and the background. Along with other static genomic features, we adopted a random forest framework to predict TF–DNA interaction. After conducting comprehensive tests, we saw that the proposed method accurately predicts TF binding and performs favorably versus competing methods.
    Keywords: Genomics
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  • 55
    Publication Date: 2012-10-10
    Description: Enriching target sequences in sequencing libraries via capture hybridization to bait/probes is an efficient means of leveraging the capabilities of next-generation sequencing for obtaining sequence data from target regions of interest. However, homologous sequences from non-target regions may also be enriched by such methods. Here we investigate the fidelity of capture enrichment for complete mitochondrial DNA (mtDNA) genome sequencing by analyzing sequence data for nuclear copies of mtDNA (NUMTs). Using capture-enriched sequencing data from a mitochondria-free cell line and the parental cell line, and from samples previously sequenced from long-range PCR products, we demonstrate that NUMT alleles are indeed present in capture-enriched sequence data, but at low enough levels to not influence calling the authentic mtDNA genome sequence. However, distinguishing NUMT alleles from true low-level mutations (e.g. heteroplasmy) is more challenging. We develop here a computational method to distinguish NUMT alleles from heteroplasmies, using sequence data from artificial mixtures to optimize the method.
    Keywords: Genomics
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  • 56
    Publication Date: 2012-10-10
    Description: Single nucleotide polymorphisms (SNPs) are increasingly used to tag genetic loci associated with phenotypes such as risk of complex diseases. Technically, this is done genome-wide without prior restriction or knowledge of biological feasibility in scans referred to as genome-wide association studies (GWAS). Depending on the linkage disequilibrium (LD) structure at a particular locus, such tagSNPs may be surrogates for many thousands of other SNPs, and it is difficult to distinguish those that may play a functional role in the phenotype from those simply genetically linked. Because a large proportion of tagSNPs have been identified within non-coding regions of the genome, distinguishing functional from non-functional SNPs has been an even greater challenge. A strategy was recently proposed that prioritizes surrogate SNPs based on non-coding chromatin and epigenomic mapping techniques that have become feasible with the advent of massively parallel sequencing. Here, we introduce an R/Bioconductor software package that enables the identification of candidate functional SNPs by integrating information from tagSNP locations, lists of linked SNPs from the 1000 genomes project and locations of chromatin features which may have functional significance. Availability: FunciSNP is available from Bioconductor (bioconductor.org).
    Keywords: Genomics
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  • 57
    Publication Date: 2014-04-15
    Description: Reconstructing the evolutionary relationships of species is a major goal in biology. Despite the increasing number of completely sequenced genomes, a large number of phylogenetic projects rely on targeted sequencing and analysis of a relatively small sample of marker genes. The selection of these phylogenetic markers should ideally be based on accurate predictions of their combined, rather than individual, potential to accurately resolve the phylogeny of interest. Here we present and validate a new phylogenomics strategy to efficiently select a minimal set of stable markers able to reconstruct the underlying species phylogeny. In contrast to previous approaches, our methodology does not only rely on the ability of individual genes to reconstruct a known phylogeny, but it also explores the combined power of sets of concatenated genes to accurately infer phylogenetic relationships of species not previously analyzed. We applied our approach to two broad sets of cyanobacterial and ascomycetous fungal species, and provide two minimal sets of six and four genes, respectively, necessary to fully resolve the target phylogenies. This approach paves the way for the informed selection of phylogenetic markers in the effort of reconstructing the tree of life.
    Keywords: Genomics
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  • 58
    Publication Date: 2016-05-20
    Description: Visualization of chromosomal dynamics is important for understanding many fundamental intra-nuclear processes. Efficient and reliable live-cell multicolor labeling of chromosomal loci can realize this goal. However, the current methods are constrained mainly by insufficient labeling throughput, efficiency, flexibility as well as photostability. Here we have developed a new approach to realize dual-color chromosomal loci imaging based on a modified single-guide RNA (sgRNA) of the CRISPR/Cas9 system. The modification of sgRNA was optimized by structure-guided engineering of the original sgRNA, consisting of RNA aptamer insertions that bind fluorescent protein-tagged effectors. By labeling and tracking telomeres, centromeres and genomic loci, we demonstrate that the new approach is easy to implement and enables robust dual-color imaging of genomic elements. Importantly, our data also indicate that the fast exchange rate of RNA aptamer binding effectors makes our sgRNA-based labeling method much more tolerant to photobleaching than the Cas9-based labeling method. This is crucial for continuous, long-term tracking of chromosomal dynamics. Lastly, as our method is complementary to other live-cell genomic labeling systems, it is therefore possible to combine them into a plentiful palette for the study of native chromatin organization and genome ultrastructure dynamics in living cells.
    Keywords: Genomics
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  • 59
    Publication Date: 2012-06-28
    Description: Environmental biosurveillance and microbial ecology studies use PCR-based assays to detect and quantify microbial taxa and gene sequences within a complex background of microorganisms. However, the fragmentary nature and growing quantity of DNA-sequence data make group-specific assay design challenging. We solved this problem by developing a software platform that enables PCR-assay design at an unprecedented scale. As a demonstration, we developed quantitative PCR assays for a globally widespread, ecologically important bacterial group in soil, Acidobacteria Group 1. A total of 33 684 Acidobacteria 16S rRNA gene sequences were used for assay design. Following 1 week of computation on a 376-core cluster, 83 assays were obtained. We validated the specificity of the top three assays, collectively predicted to detect 42% of the Acidobacteria Group 1 sequences, by PCR amplification and sequencing of DNA from soil. Based on previous analyses of 16S rRNA gene sequencing, Acidobacteria Group 1 species were expected to decrease in response to elevated atmospheric CO 2 . Quantitative PCR results, using the Acidobacteria Group 1-specific PCR assays, confirmed the expected decrease and provided higher statistical confidence than the 16S rRNA gene-sequencing data. These results demonstrate a powerful capacity to address previously intractable assay design challenges.
    Keywords: Genomics
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  • 60
    Publication Date: 2012-08-08
    Description: Due to dramatic advances in DNA technology, quantitative measures of annotation data can now be obtained in continuous coordinates across the entire genome, allowing various heterogeneous ‘genomic landscapes’ to emerge. Although much effort has been devoted to comparing DNA sequences, not much attention has been given to comparing these large quantities of data comprehensively. In this article, we introduce a method for rapidly detecting local regions that show high correlations between genomic landscapes. We overcame the size problem for genome-wide data by converting the data into series of symbols and then carrying out sequence alignment. We also decomposed the oscillation of the landscape data into different frequency bands before analysis, since the real genomic landscape is a mixture of embedded and confounded biological processes working at different scales in the cell nucleus. To verify the usefulness and generality of our method, we applied our approach to well investigated landscapes from the human genome, including several histone modifications. Furthermore, by applying our method to over 20 genomic landscapes in human and 12 in mouse, we found that DNA replication timing and the density of Alu insertions are highly correlated genome-wide in both species, even though the Alu elements have amplified independently in the two genomes. To our knowledge, this is the first method to align genomic landscapes at multiple scales according to their shape.
    Keywords: Genomics
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  • 61
    Publication Date: 2013-03-13
    Description: The numerous discovered cases of domesticated transposable element (TE) proteins led to the recognition that TEs are a significant source of evolutionary innovation. However, much less is known about the reverse process, whether and to what degree the evolution of TEs is influenced by the genome of their hosts. We addressed this issue by searching for cases of incorporation of host genes into the sequence of TEs and examined the systems-level properties of these genes using the Saccharomyces cerevisiae and Drosophila melanogaster genomes. We identified 51 cases where the evolutionary scenario was the incorporation of a host gene fragment into a TE consensus sequence, and we show that both the yeast and fly homologues of the incorporated protein sequences have central positions in the cellular networks. An analysis of selective pressure (Ka/Ks ratio) detected significant selection in 37% of the cases. Recent research on retrovirus-host interactions shows that virus proteins preferentially target hubs of the host interaction networks enabling them to take over the host cell using only a few proteins. We propose that TEs face a similar evolutionary pressure to evolve proteins with high interacting capacities and take some of the necessary protein domains directly from their hosts.
    Keywords: Genomics
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  • 62
    Publication Date: 2016-11-01
    Description: Presence of excess unaltered, wild-type (WT) DNA providing no information of biological or clinical value often masks rare alterations containing diagnostic or therapeutic clues in cancer, prenatal diagnosis, infectious diseases or organ transplantation. With the surge of high-throughput technologies there is a growing demand for removing unaltered DNA over large pools-of-sequences. Here we present nuclease-assisted minor-allele enrichment with probe-overlap (NaME-PrO), a single-step approach with broad genome coverage that can remove WT-DNA from numerous sequences simultaneously, prior to genomic analysis. NaME-PrO employs a double-strand-DNA-specific nuclease and overlapping oligonucleotide-probes interrogating WT-DNA targets and guiding nuclease digestion to these sites. Mutation-containing DNA creates probe-DNA mismatches that inhibit digestion, thus subsequent DNA-amplification magnifies DNA-alterations at all selected targets. We demonstrate several-hundred-fold mutation enrichment in diverse human samples on multiple clinically relevant targets including tumor samples and circulating DNA in 50-plex reactions. Enrichment enables routine mutation detection at 0.01% abundance while by adjusting conditions it is possible to sequence mutations down to 0.00003% abundance, or to scan tumor-suppressor genes for rare mutations. NaME-PrO introduces a simple and highly parallel process to remove un-informative DNA sequences and unmask clinically and biologically useful alterations.
    Keywords: Genomics
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  • 63
    Publication Date: 2012-10-24
    Description: A number of studies have shown that transcriptome analysis in terms of chromosomal location can reveal regions of non-random transcriptional activity within the genome. Genomic clusters of differentially expressed genes can identify genomic patterns of structural organization, underlying copy number variations or long-range epigenetic regulation such as X-chromosome inactivation. Here we apply an integrative bioinformatics analysis to a collection of 315 freely available mouse pluripotent stem cell samples to discover transcriptional clusters in the genome. We show that over half of the analysed samples (56.83%) carry whole or partial-chromosome spanning clusters which recur in genomic regions previously implicated in chromosomal imbalances. Strikingly, we found that the presence of such large-clusters is linked to the differential expression of a limited number of genes, common to all samples carrying clusters irrespectively of the chromosome where the cluster is found. We have used these genes to train and test classification models that can predict samples that carry large-scale clusters on any chromosome with over 90% accuracy. Our findings suggest that there is a common downstream activation in these cells that affects a limited number of nodes. We propose that this effect is linked to selective advantage and identify potential driver genes.
    Keywords: Genomics
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  • 64
    Publication Date: 2012-11-04
    Description: The rapidly growing amount of genomic sequence data being generated and made publicly available necessitate the development of new data storage and archiving methods. The vast amount of data being shared and manipulated also create new challenges for network resources. Thus, developing advanced data compression techniques is becoming an integral part of data production and analysis. The HapMap project is one of the largest public resources of human single-nucleotide polymorphisms (SNPs), characterizing over 3 million SNPs genotyped in over 1000 individuals. The standard format and biological properties of HapMap data suggest that a dedicated genetic compression method can outperform generic compression tools. We propose a compression methodology for genetic data by introducing H ap Z ipper , a lossless compression tool tailored to compress HapMap data beyond benchmarks defined by generic tools such as gzip , bzip2 and lzma . We demonstrate the usefulness of H ap Z ipper by compressing HapMap 3 populations to 〈5% of their original sizes. H ap Z ipper is freely downloadable from https://bitbucket.org/pchanda/hapzipper/downloads/HapZipper.tar.bz2 .
    Keywords: Genomics
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  • 65
    Publication Date: 2012-11-04
    Description: Spliced alignment plays a central role in the precise identification of eukaryotic gene structures. Even though many spliced alignment programs have been developed, recent rapid progress in DNA sequencing technologies demands further improvements in software tools. Benchmarking algorithms under various conditions is an indispensable task for the development of better software; however, there is a dire lack of appropriate datasets usable for benchmarking spliced alignment programs. In this study, we have constructed two types of datasets: simulated sequence datasets and actual cross-species datasets. The datasets are designed to correspond to various real situations, i.e. divergent eukaryotic species, different types of reference sequences, and the wide divergence between query and target sequences. In addition, we have developed an extended version of our program Spaln , which incorporates two additional features to the scoring scheme of the original version, and examined this extended version, Spaln2, together with the original Spaln and other representative aligners based on our benchmark datasets. Although the effects of the modifications are not individually striking, Spaln2 is consistently most accurate and reasonably fast in most practical cases, especially for plants and fungi and for increasingly divergent pairs of target and query sequences.
    Keywords: Genomics
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  • 66
    Publication Date: 2013-05-04
    Description: Various ‘omics’ technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.
    Keywords: Genomics
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  • 67
    Publication Date: 2013-04-14
    Description: Multiplex analytical systems that allow detection of multiple nucleic acid targets in one assay can provide rapid characterization of a sample while still saving cost and resources. However, few systems have proven to offer a solution for mid-plex (e.g. 10- to 50-plex) analysis that is high throughput and cost effective. Here we describe the combined use of fluorescence color and melting temperature (T m ) as a virtual 2D label that enables homogenous detection of one order of magnitude more targets than current strategies on real-time polymerase chain reaction platform. The target was first hybridized with a pair of ligation oligonucleotides, one of which harbored an artificial sequence that had a unique T m when hybridized with a reporter fluorogenic probe. The ligated products were then amplified by a universal primer pair and denatured by a melting curve analysis procedure. The targets were identified by their respective T m values in the corresponding fluorescence detection channels. The proof-of-principle of this approach was validated by genotyping 15 high-risk human papillomaviruses and 48 human single-nucleotide polymorphisms. The robustness of this method was demonstrated by analyzing a large number of clinical samples in both cases. The combined merits of multiplexity, flexibility and simplicity should make this approach suitable for a variety of applications.
    Keywords: Genomics
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  • 68
    Publication Date: 2012-11-25
    Description: The chromatin structure of eukaryotic telomeres plays an essential role in telomere functions. However, their study might be impaired by the presence of interstitial telomeric sequences (ITSs), which have a widespread distribution in different model systems. We have developed a simple approach to study the chromatin structure of Arabidopsis telomeres independently of ITSs by analyzing ChIP-seq data. This approach could be used to study the chromatin structure of telomeres in some other eukaryotes. The analysis of ChIP-seq experiments revealed that Arabidopsis telomeres have higher density of histone H3 than centromeres, which might reflects their short nucleosomal organization. These experiments also revealed that Arabidopsis telomeres have lower levels of heterochromatic marks than centromeres (H3K9 Me2 and H3K27 Me ), higher levels of some euchromatic marks (H3K4 Me2 and H3K9Ac) and similar or lower levels of other euchromatic marks (H3K4 Me3 , H3K36 Me2 , H3K36 Me3 and H3K18Ac). Interestingly, the ChIP-seq experiments also revealed that Arabidopsis telomeres exhibit high levels of H3K27 Me3 , a repressive mark that associates with many euchromatic genes. The epigenetic profile of Arabidopsis telomeres is closely related to the previously defined chromatin state 2. This chromatin state is found in 23% of Arabidopsis genes, many of which are repressed or lowly expressed. At least, in part, this scenario is similar in rice.
    Keywords: Genomics
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  • 69
    Publication Date: 2015-08-18
    Description: Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/ .
    Keywords: Genomics
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  • 70
    Publication Date: 2015-08-18
    Description: Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 71
    Publication Date: 2015-08-18
    Description: Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff , (M1) and Hivep1, Nfil3, Prdm1 , (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 72
    Publication Date: 2016-12-01
    Description: The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused and dependent on ‘non-core’ portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity and reveals a novel role for the RAG1 non-core region in RAG1 targeting.
    Keywords: Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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