ALBERT

Description: Overpressure and buoyant effect of underlying sediments are generally used to account for the upward motion or formation of submarine mud volcanoes and mud diapirs. In this study, we process and interpret the gravity anomalies associated with the active mud diapirs off SW Taiwan. Geologically, the mud diapirs are just formed and are still very active, thus we can better understand the initial process of the mud diapirs formation through the gravity analysis. Our results show that the density contrasts of the submarine mud diapirs with respect to the surroundings are generally positive. Because the study area is in a tectonically compressive regime and the gas plume venting from the submarine mud volcanoes is very active, we thus infer that mechanically the mud diapirs off SW Taiwan have been formed mainly due to the tectonic compression on the underlying sediments of high pore-fluid pressure, instead of the buoyancy of the buried sediments. The overpressured sediments and fluid are compressed and pushed upwards to pierce the overlying sediments and form the more compacted mud diapirs. The relatively denser material of the mud diapirs probably constrains the flowing courses of the submarine canyons off SW Taiwan, especially for the upper reaches of the Kaoping and Fangliao submarine canyons.

Description: Aims Clear-cutting is a common forest management practice, especially in subtropical China. However, the potential ecological consequences of clear-cutting remain unclear. In particular, the effect of clear-cutting on soil processes, such as the carbon cycle, has not been quantified in subtropical forests. Here, we investigated the response of soil respiration (Rs) to clear-cutting during a 12-month period in a subtropical forest in eastern China. Methods We randomly selected four clear-cut (CC) plots and four corresponding undisturbed forest (UF) plots. Measurements of Rs were made at monthly time points and were combined with continuous climatic measurements in both CC and UF. Daily Rs was estimated by interpolating data with an exponential model dependent on soil temperature. Daily Rs was cumulated to annual Rs estimates. Important Findings In the first year after clear-cutting, annual estimates of Rs in CC (508±23g C m –2 yr –1 ) showed no significant difference to UF plots (480±12g C m –2 yr –1 ). During the summer, soil temperatures were usually higher, whereas the soil volumetric water content was lower in CC than in UF plots. The long-term effects of clear-cutting on Rs are not significant, although there might be effects during the first several months after clear-cutting. Compared with previous work, this pattern was more pronounced in our subtropical forest than in the temperate and boreal forests that have been studied by others. With aboveground residuals off-site after clear-cutting, our results indicate that the stimulation of increasing root debris, as well as environmental changes, will not lead to a significant increase in Rs. In addition, long-term Rs will not show a significant decrease from the termination of root respiration, and this observation might be because of the influence of fast-growing vegetation after clear-cutting in situ .

Description: Motivation: Fragmented RNA immunoprecipitation combined with RNA sequencing enabled the unbiased study of RNA epigenome at a near single-base resolution; however, unique features of this new type of data call for novel computational techniques. Result: Through examining the connections of RNA epigenome sequencing data with two well-studied data types, ChIP-Seq and RNA-Seq, we unveiled the salient characteristics of this new data type. The computational strategies were discussed accordingly, and a novel data processing pipeline was proposed that combines several existing tools with a newly developed exome-based approach ‘exomePeak’ for detecting, representing and visualizing the post-transcriptional RNA modification sites on the transcriptome. Availability: The MATLAB package ‘exomePeak’ and additional details are available at http://compgenomics.utsa.edu/exomePeak/ . Contact: yufei.huang@utsa.edu or jmeng@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: N 6 -methyl-adenosine (m 6 A) is the most prevalent mRNA methylation but precise prediction of its mRNA location is important for understanding its function. A recent sequencing technology, known as Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq), has been developed for transcriptome-wide profiling of m 6 A. We previously developed a peak calling algorithm called exomePeak. However, exomePeak over-simplifies data characteristics and ignores the reads’ variances among replicates or reads dependency across a site region. To further improve the performance, new model is needed to address these important issues of MeRIP-seq data. Results: We propose a novel, graphical model-based peak calling method, MeTPeak, for transcriptome-wide detection of m 6 A sites from MeRIP-seq data. MeTPeak explicitly models read count of an m 6 A site and introduces a hierarchical layer of Beta variables to capture the variances and a Hidden Markov model to characterize the reads dependency across a site. In addition, we developed a constrained Newton’s method and designed a log-barrier function to compute analytically intractable, positively constrained Beta parameters. We applied our algorithm to simulated and real biological datasets and demonstrated significant improvement in detection performance and robustness over exomePeak. Prediction results on publicly available MeRIP-seq datasets are also validated and shown to be able to recapitulate the known patterns of m 6 A, further validating the improved performance of MeTPeak. Availability and implementation: The package ‘MeTPeak’ is implemented in R and C ++, and additional details are available at https://github.com/compgenomics/MeTPeak Contact: yufei.huang@utsa.edu or xdchoi@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

Description: We have developed and implemented an iterative algorithm of flux calibration for the LAMOST Spectroscopic Survey of the Galactic anticentre (LSS-GAC). For a given LSS-GAC plate, the spectra are first processed with a set of nominal spectral response curves (SRCs) and used to derive initial stellar atmospheric parameters (effective temperature T eff , surface gravity log  g and metallicity [Fe/H]) as well as dust reddening E ( B  –  V ) of all targeted stars. For each of the 16 spectrographs, several F-type stars with good signal-to-noise ratios are selected as flux standard stars for further, iterative spectral flux calibration. Comparison of spectrophotometric colours, deduced from the flux-calibrated spectra, with the photometric measurements yield average differences of 0.02 ± 0.07 and –0.04 ± 0.09 mag for ( g  –  r ) and ( g  –  i ), respectively. The relatively large negative offset in ( g  –  i ) is because we have opted not to correct for the telluric bands, most notably the atmospheric A band in the wavelength range of the i band. Comparison of LSS-GAC multi-epoch observations of duplicate targets indicates that the algorithm has achieved an accuracy of about 10 per cent in relative flux calibration for the wavelength range 4000–9000 Å. The shapes of SRCs deduced for individual LAMOST spectrographs vary by up to 30 per cent for a given night, and larger for different nights, indicating that the derivation of SRCs for the individual plates is essential to achieve accurate flux calibration for the LAMOST spectra.

Description: Urofacial syndrome (UFS) is an autosomal recessive disease with severe dysfunctional urination including urinary incontinence (UI). Biallelic mutations of HPSE2 are discovered from UFS patients, suggesting that HPSE2 is a candidate disease gene. Here, we show that deletion of Hpse2 is sufficient to cause the UFS-like phenotype in mice. Hpse2 knockout mutants display a distended bladder (megacystis) phenotype and abnormal voiding behavior similar to that found in patients. While Hpse2 is largely dispensable for detrusor smooth muscle and urothelial cell fate determination, the mutants have significantly lower rates of cell proliferation than wild-type littermate controls. All Hpse2 mutants have a growth retardation phenotype and die within a month after birth. Comprehensive blood chemistry and urinalysis indicate that Hpse2 mutants have renal dysfunction and malnutrition. We provide evidence that transforming growth factor beta ( Tgfβ ) signaling is attenuated at birth. However, Tgfβ activity is significantly enhanced at later stages when the urological phenotype is severe, and the mutant bladders have accumulated excessive amount of fibrotic tissue. Together, these findings strongly suggest that Hpse2 is a causative gene of human UFS and further uncover unexpected roles of Hpse2 in bladder physiology, tissue remodeling and Tgfβ signaling.

Description: Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/methylation/ ) is the first comprehensive resource for N6-methyladenosine (m 6 A) in mammalian transcriptome. It includes a database that records publicaly available data sets from methylated RNA immunoprecipitation sequencing (MeRIP-Seq), a recently developed technology for interrogating m 6 A methyltranscriptome. MeT-DB includes ~300k m 6 A methylation sites in 74 MeRIP-Seq samples from 22 different experimental conditions predicted by exomePeak and MACS2 algorithms. To explore this rich information, MeT-DB also provides a genome browser to query and visualize context-specific m 6 A methylation under different conditions. MeT-DB also includes the binding site data of microRNA, splicing factor and RNA binding proteins in the browser window for comparison with m 6 A sites and for exploring the potential functions of m 6 A. Analysis of differential m 6 A methylation and the related differential gene expression under two conditions is also available in the browser. A global perspective of the genome-wide distribution of m 6 A methylation in all the data is provided in circular ideograms, which also act as a navigation portal. The query results and the entire data set can be exported to assist publication and additional analysis.

Description: The RNA transcriptome varies in response to cellular differentiation as well as environmental factors, and can be characterized by the diversity and abundance of transcript isoforms. Differential transcription analysis, the detection of differences between the transcriptomes of different cells, may improve understanding of cell differentiation and development and enable the identification of biomarkers that classify disease types. The availability of high-throughput short-read RNA sequencing technologies provides in-depth sampling of the transcriptome, making it possible to accurately detect the differences between transcriptomes. In this article, we present a new method for the detection and visualization of differential transcription. Our approach does not depend on transcript or gene annotations. It also circumvents the need for full transcript inference and quantification, which is a challenging problem because of short read lengths, as well as various sampling biases. Instead, our method takes a divide-and-conquer approach to localize the difference between transcriptomes in the form of alternative splicing modules (ASMs), where transcript isoforms diverge. Our approach starts with the identification of ASMs from the splice graph, constructed directly from the exons and introns predicted from RNA-seq read alignments. The abundance of alternative splicing isoforms residing in each ASM is estimated for each sample and is compared across sample groups. A non-parametric statistical test is applied to each ASM to detect significant differential transcription with a controlled false discovery rate. The sensitivity and specificity of the method have been assessed using simulated data sets and compared with other state-of-the-art approaches. Experimental validation using qRT-PCR confirmed a selected set of genes that are differentially expressed in a lung differentiation study and a breast cancer data set, demonstrating the utility of the approach applied on experimental biological data sets. The software of DiffSplice is available at http://www.netlab.uky.edu/p/bioinfo/DiffSplice .

Description: The specificities of glycosaminoglycan (GAG) modification enzymes, particularly sulfotransferases, and the locations and concentrations of these enzymes in the Golgi apparatus give rise to the mature GAG polysaccharides that bind protein ligands. We studied the substrate specificities of sulfotransferases with a stable isotopically labeled donor substrate, 3'-phosphoadenosine-5'-phosphosulfate. The sulfate incorporated by in vitro sulfation using recombinant sulfotransferases was easily distinguished from those previously present on the GAG chains using mass spectrometry. The enrichment of the [M + 2] isotopic peak caused by 34 S incorporation, and the [M + 2]/[M + 1] ratio, provided reliable and sensitive measures of the degree of in vitro sulfation. It was found that both CHST3 and CHST15 have higher activities at the non-reducing end (NRE) units of chondroitin sulfate, particularly those terminating with a GalNAc monosaccharide. In contrast, both NDST1 and HS6ST1 showed lower activities at the NRE of heparan sulfate (HS) chains than at the interior of the chain. Contrary to the traditional view of HS biosynthesis processes, NDST1 also showed activity on O -sulfated GlcNAc residues.

Description: Motivation: Copy number abbreviation (CNA) is one type of genomic aberration that is often induced by genome instability and is associated with diseases such as cancer. Determination of the genome-wide CNA profile is an important step in identifying the underlying mutation mechanisms. Genomic data based on next-generation sequencing technology are particularly suitable for determination of high-quality CNA profile. Now is an important time to reevaluate the use of sequencing techniques for CNA analysis, especially with the rapid growth of the different targeted genome and whole-genome sequencing strategies. Results: In this study, we provide a comparison of resequencing strategies, with regard to their utility, applied to the same hepatocellular carcinoma sample for copy number determination. These strategies include whole-genome, exome and restriction site-associated DNA (RAD) sequencing. The last of these strategies is a targeted sequencing technique that involves cutting the genome with a restriction enzyme and isolating the targeted sequences. Our data demonstrate that RAD sequencing is an efficient and comprehensive strategy that allows the cost-effective determination of CNAs. Further investigation of RAD sequencing data led to the finding that a precise measurement of the allele frequency would be a helpful complement to the read depth for CNA analysis for two reasons. First, knowledge of the allele frequency helps to resolve refined calculations of allele-specific copy numbers, which, in turn, identify the functionally important CNAs that are under natural selection on the parental alleles. Second, this knowledge enables deconvolution of CNA patterns in complex genomic regions. Contact: juncai@big.ac.cn or ciwu@uchicago.edu Supplementary information: Supplementary data are available at Bioinformatics online.