PaperPlayer biorxiv bioinformatics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.06.328559v1?rss=1

Authors: Farrell, C., Thompson, M., Tosevska, A., Oyetunde, A., Pellegrini, M.

Abstract:

Background: Bisulfite sequencing is commonly employed to measure DNA methylation. Processing bisulfite sequencing data is often challenging due to the computational demands of mapping a low complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt); a fast and scalable bisulfite sequencing analysis platform. Findings: We evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. Conclusion:BSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a python package and command line utility for flexibility when building informatics pipelines. BSBolt is available at https://github.com/NuttyLogic/BSBolt under a MIT license.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.06.328674v1?rss=1

Authors: Zhao, N., Boyle, A. P.

Abstract:

Genomic and epigenomic features are captured at a genome-wide level by using high-throughput sequencing technologies. Peak calling is one of the first essential steps in analyzing these features by delineating regions such as open chromatin regions and transcription factor binding sites. Our original peak calling software, F-Seq, has been widely used and shown to be the most sensitive and accurate peak caller for DNase I hypersensitive sites sequencing (DNase-seq) data. However, F-Seq lacks support for user-input control dataset nor reporting test statistics, limiting its ability to capture systematic and experimental biases and accurately estimate background distributions. Here we present an improved version, F-Seq2, which combined the power of kernel density estimation and a dynamic "continuous" Poisson distribution to robustly account for local biases and solve ties when ranking candidate peaks. In F-score and motif distance analysis, we demonstrated the superior performance of F-Seq2 than other competing peak callers used by the ENCODE Consortium on simulated and real ATAC-seq and ChIP-seq datasets. The output of F-Seq2 is suitable for irreproducible discovery rate (IDR) analysis as the test statistics calculated for individual candidate summit and ties are robustly solved.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.08.331017v1?rss=1

Authors: Geuther, B. Q., Peer, A., He, H., Sabnis, G., Philip, V. M., Kumar, V.

Abstract:

Automated detection of complex animal behaviors remains a challenging problem in neuroscience, particularly for behaviors that consist of disparate sequential motions. Grooming, a prototypical stereotyped behavior, is often used as an endophenotype in psychiatric genetics. Using mouse grooming behavior as an example, we develop a general purpose neural network architecture capable of dynamic action detection at human observer-level performance and operate across dozens of mouse strains with high visual diversity. We provide insights into the amount of human annotated training data that are needed to achieve such performance. We survey grooming behavior in the open field in ~2500 mice across 62 strains, determine its heritable components, conduct GWAS to outline its genetic architecture, and perform PheWAS to link human psychiatric traits through shared underlying genetics. Our general machine learning solution that automatically classifies complex behaviors in large datasets will facilitate systematic studies of mechanisms underlying these behaviors.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.07.330563v1?rss=1

Authors: Ranjan, B., Sun, W., Park, J., Xie, R., Alipour, F., Singhal, V., Prabhakar, S.

Abstract:

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. However, we found that the performance of existing feature selection methods was inconsistent across benchmark datasets, and occasionally even worse than without feature selection. Moreover, existing methods ignored information contained in gene-gene correlations. We therefore developed DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. In a published scRNA-seq dataset from sorted monocytes, DUBStepR sensitively detected a rare and previously invisible population of contaminating basophils. DUBStepR is scalable to large datasets, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.08.331322v1?rss=1

Authors: Sheffield, N. C., Stolarczyk, M., Reuter, V. P., Rendeiro, A.

Abstract:

Organizing and annotating biological sample data is critical in data-intensive bioinformatics. Unfortunately, incompatibility is common between metadata format of a data source and that required by a processing tool. There is no broadly accepted standard to organize metadata across biological projects and bioinformatics tools, restricting the portability and reusability of both annotated datasets and analysis software. To address this, we present Portable Encapsulated Projects (PEP), a formal specification for biological sample metadata structure. The PEP specification accommodates typical features of data-intensive bioinformatics projects with many samples, whether from individual experiments, organisms, or single cells. In addition to standardization, the PEP specification provides descriptors and modifiers for different organizational layers of a project, which improve portability among computing environments and facilitate use of different processing tools. PEP includes a schema validator framework, allowing formal definition of required metadata attributes for any type of biomedical data analysis. We have implemented packages for reading PEPs in both Python and R to provide a language-agnostic interface for organizing project metadata. PEP therefore presents an important step toward unifying data annotation and processing tools in data-intensive biological research projects.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.08.330985v1?rss=1

Authors: Seiler, E., Mehringer, S., Darvish, M., Turc, E., Reinert, K.

Abstract:

We present Raptor, a tool for approximately searching many queries in large collections of nucleotide sequences. In comparison with similar tools like Mantis and COBS, Raptor is 12 - 144 times faster and uses up to 30 times less memory. Raptor uses winnowing minimizers to define a set of representative k-mers, an extension of the Interleaved Bloom Filters (IBF) as a set membership data structure, and probabilistic thresholding for minimizers. Our approach allows compression and a partitioning of the IBF to enable the effective use of secondary memory.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.07.325332v1?rss=1

Authors: Shen, Y., Kingsford, C.

Abstract:

Three-dimensional chromosomal structure plays an important role in gene regulation. Chromosome conformation capture techniques, especially the high-throughput, sequencing-based technique Hi-C, provide new insights on spatial architectures of chromosomes. However, Hi-C data contains artifacts and systemic biases that substantially influence subsequent analysis. Computational models have been developed to address these biases explicitly, however, it is difficult to enumerate and eliminate all the biases in models. Other models are designed to correct biases implicitly, but they will also be invalid in some situations such as copy number variations. New methods are required for better bias correction. We characterize a new kind of artifact in Hi-C data. We find that this artifact is caused by incorrect alignment of Hi-C reads against approximate repeat regions and can lead to erroneous chromatin contact signals. The artifact cannot be corrected by current Hi-C correction methods. We design a probabilistic method and develop a new Hi-C processing pipeline by integrating our probabilistic method with the HiC-Pro pipeline. We find that the new pipeline can remove this new artifact effectively, while preserving important features of the original Hi-C matrices.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.06.328328v1?rss=1

Authors: Nicholls, S. M., Poplawski, R., Bull, M. J., Underwood, A., Chapman, M., Abu-Dahab, K., Taylor, B., Jackson, B., Rey, S., Amato, R., Livett, R., Goncalves, S., Harrison, E. M., Peacock, S. J., Aanensen, D. M., Rambaut, A., Connor, T. R., Loman, N. J., The COVID-19 Genomics UK Consortium (COG-UK)

Abstract:

Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense sampling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.07.329516v1?rss=1

Authors: Schulz, C., Almaas, E.

Abstract:

Approaches for systematizing information of relatedness between organisms is important in biology. Phylogenetic analyses based on sets of highly conserved genes are currently the basis for the Tree of Life. Genome-scale metabolic reconstructions contain high-quality information regarding the metabolic capability of an organism and are typically restricted to metabolically active enzyme-encoding genes. While there are many tools available to generate draft reconstructions, expert-level knowledge is still required to generate and manually curate high-quality genome-scale metabolic models and to fill gaps in their reaction networks. Here, we use the tool AutoKEGGRec to construct $975$ genome-scale metabolic draft reconstructions encoded in the KEGG database without further curation. The organisms are selected across all three domains, and their metabolic networks serve as basis for generating phylogenetic trees. We find that using all reactions encoded, these metabolism-based comparisons give rise to a phylogenetic tree with close similarity to the Tree of Life. While this tree is quite robust to reasonable levels of noise in the metabolic reaction content of an organism, we find a significant heterogeneity in how much noise an organism may tolerate before it is incorrectly placed in the tree. Furthermore, by using the protein sequences for particular metabolic functions and pathway sets, such as central carbon-, nitrogen-, and sulfur-metabolism, as basis for the organism comparisons, we generate highly specific phylogenetic trees. We believe the generation of phylogenetic trees based on metabolic reaction content, in particular when focused on specific functions and pathways, could aid the identification of functionally important metabolic enzymes and be of value for genome-scale metabolic modellers and enzyme-engineers.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.06.328039v1?rss=1

Authors: Prost, J. A., Cameron, C. J., Blanchette, M.

Abstract:

Genomic organization is critical for proper gene regulation and based on a hierarchical model, where chromosomes are segmented into megabase-sized, cell-type-specific transcriptionally active (A) and inactive (B) compartments. Here, we describe SACSANN, a machine learning pipeline consisting of stacked artificial neural networks that predicts compartment annotation solely from genomic sequence-based features such as predicted transcription factor binding sites and transposable elements. SACSANN provides accurate and cell-type specific compartment predictions, while identifying key genomic sequence determinants that associate with A/B compartments. Models are shown to be largely transferable across analogous human and mouse cell types. By enabling the study of chromosome compartmentalization in species for which no Hi-C data is available, SACSANN paves the way toward the study of 3D genome evolution. SACSANN is publicly available on GitHub: https://github.com/BlanchetteLab/SACSANN

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