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  • 1
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    Modeling shocks in massive transportation systems [Statistics] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-05-06
    Description: Public transportation systems are an essential component of major cities. The widespread use of smart cards for automated fare collection in these systems offers a unique opportunity to understand passenger behavior at a massive scale. In this study, we use network-wide data obtained from smart cards in the London transport...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Systems-level dynamic analyses of fate change in murine embryonic stem cells (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-11-20
    Description: Molecular regulation of embryonic stem cell (ESC) fate involves a coordinated interaction between epigenetic, transcriptional and translational mechanisms. It is unclear how these different molecular regulatory mechanisms interact to regulate changes in stem cell fate. Here we present a dynamic systems-level study of cell fate change in murine ESCs following a well-defined perturbation. Global changes in histone acetylation, chromatin-bound RNA polymerase II, messenger RNA (mRNA), and nuclear protein levels were measured over 5 days after downregulation of Nanog, a key pluripotency regulator. Our data demonstrate how a single genetic perturbation leads to progressive widespread changes in several molecular regulatory layers, and provide a dynamic view of information flow in the epigenome, transcriptome and proteome. We observe that a large proportion of changes in nuclear protein levels are not accompanied by concordant changes in the expression of corresponding mRNAs, indicating important roles for translational and post-translational regulation of ESC fate. Gene-ontology analysis across different molecular layers indicates that although chromatin reconfiguration is important for altering cell fate, it is preceded by transcription-factor-mediated regulatory events. The temporal order of gene expression alterations shows the order of the regulatory network reconfiguration and offers further insight into the gene regulatory network. Our studies extend the conventional systems biology approach to include many molecular species, regulatory layers and temporal series, and underscore the complexity of the multilayer regulatory mechanisms responsible for changes in protein expression that determine stem cell fate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199216/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199216/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Rong -- Markowetz, Florian -- Unwin, Richard D -- Leek, Jeffrey T -- Airoldi, Edoardo M -- MacArthur, Ben D -- Lachmann, Alexander -- Rozov, Roye -- Ma'ayan, Avi -- Boyer, Laurie A -- Troyanskaya, Olga G -- Whetton, Anthony D -- Lemischka, Ihor R -- P50 GM071558/GM/NIGMS NIH HHS/ -- P50 GM071558-01A20007/GM/NIGMS NIH HHS/ -- P50 GM071558-020007/GM/NIGMS NIH HHS/ -- P50 GM071558-030007/GM/NIGMS NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2009 Nov 19;462(7271):358-62. doi: 10.1038/nature08575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. rlu@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924215" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Embryonic Stem Cells/*cytology/*metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Mice ; Proteome ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Tree preserving embedding (2011)
    National Academy of Sciences
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    Publication Date: 2011-09-26
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    Reconceptualizing the classification of PNAS articles (2010)
    National Academy of Sciences
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    Publication Date: 2010-11-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Social network formation and dynamics [Statistics] (2015)
    National Academy of Sciences
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    Publication Date: 2015-05-27
    Description: Social networks affect many aspects of life, including the spread of diseases, the diffusion of information, the workers' productivity, and consumers' behavior. Little is known, however, about how these networks form and change. Estimating causal effects and mechanisms that drive social network formation and dynamics is challenging because of the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Quantitative visualization of alternative exon expression from RNA-seq data (2015)
    Oxford University Press
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    Publication Date: 2015-07-09
    Description: Motivation: Analysis of RNA sequencing (RNA-Seq) data revealed that the vast majority of human genes express multiple mRNA isoforms, produced by alternative pre-mRNA splicing and other mechanisms, and that most alternative isoforms vary in expression between human tissues. As RNA-Seq datasets grow in size, it remains challenging to visualize isoform expression across multiple samples. Results: To help address this problem, we present Sashimi plots, a quantitative visualization of aligned RNA-Seq reads that enables quantitative comparison of exon usage across samples or experimental conditions. Sashimi plots can be made using the Broad Integrated Genome Viewer or with a stand-alone command line program. Availability and implementation: Software code and documentation freely available here: http://miso.readthedocs.org/en/fastmiso/sashimi.html Contact: mesirov@broadinstitute.org , airoldi@fas.harvard.edu or cburge@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 7
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    Tree preserving embedding [Statistics] (2011)
    National Academy of Sciences
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    Publication Date: 2011-10-12
    Description: The goal of dimensionality reduction is to embed high-dimensional data in a low-dimensional space while preserving structure in the data relevant to exploratory data analysis such as clusters. However, existing dimensionality reduction methods often either fail to separate clusters due to the crowding problem or can only separate clusters at a single resolution. We develop a new approach to dimensionality reduction: tree preserving embedding. Our approach uses the topological notion of connectedness to separate clusters at all resolutions. We provide a formal guarantee of cluster separation for our approach that holds for finite samples. Our approach requires no parameters and can handle general types of data, making it easy to use in practice and suggesting new strategies for robust data visualization.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Stochastic blockmodels with a growing number of classes (2012)
    Oxford University Press
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    Publication Date: 2012-05-22
    Description: We present asymptotic and finite-sample results on the use of stochastic blockmodels for the analysis of network data. We show that the fraction of misclassified network nodes converges in probability to zero under maximum likelihood fitting when the number of classes is allowed to grow as the root of the network size and the average network degree grows at least poly-logarithmically in this size. We also establish finite-sample confidence bounds on maximum-likelihood blockmodel parameter estimates from data comprising independent Bernoulli random variates; these results hold uniformly over class assignment. We provide simulations verifying the conditions sufficient for our results, and conclude by fitting a logit parameterization of a stochastic blockmodel with covariates to a network data example comprising self-reported school friendships, resulting in block estimates that reveal residual structure.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 9
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    Estimating Selection on Synonymous Codon Usage from Noisy Experimental Data (2013)
    Oxford University Press
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    Publication Date: 2013-05-10
    Description: A key goal in molecular evolution is to extract mechanistic insights from signatures of selection. A case study is codon usage, where despite many recent advances and hypotheses, two longstanding problems remain: the relative contribution of selection and mutation in determining codon frequencies and the relative contribution of translational speed and accuracy to selection. The relevant targets of selection—the rate of translation and of mistranslation of a codon per unit time in the cell—can only be related to mechanistic properties of the translational apparatus if the number of transcripts per cell is known, requiring use of gene expression measurements. Perhaps surprisingly, different gene-expression data sets yield markedly different estimates of selection. We show that this is largely due to measurement noise, notably due to differences between studies rather than instrument error or biological variability. We develop an analytical framework that explicitly models noise in expression in the context of the population-genetic model. Estimates of mutation and selection strength in budding yeast produced by this method are robust to the expression data set used and are substantially higher than estimates using a noise-blind approach. We introduce per-gene selection estimates that correlate well with previous scoring systems, such as the codon adaptation index, while now carrying an evolutionary interpretation. On average, selection for codon usage in budding yeast is weak, yet our estimates show that genes range from virtually unselected to average per-codon selection coefficients above the inverse population size. Our analytical framework may be generally useful for distinguishing biological signals from measurement noise in other applications that depend upon measurements of gene expression.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Stochastic blockmodels with a growing number of classes (2012)
    Oxford University Press
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    Publication Date: 2012-04-17
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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