1,720,965 research outputs found
Locityper test data
No full text<p>Please find dataset description and instructions at <a href="https://locityper.vercel.app">locityper.vercel.app</a> or at <a href="https://github.com/tprodanov/locityper">github.com/tprodanov/locityper</a></p>
Read Mapping, Variant Calling, and Copy Number Variation Detection in Segmental Duplications
Full text linkSegmental duplications or low-copy repeats (LCRs) are long segments of duplicated DNA that cover more than 5% of the human genome and overlap more than 600 protein-coding genes. Copy number and sequence variants in over 150 such duplicated genes (e.g. SMN1/2, STRC, NCF1) are associated with risk for rare and complex human diseases. Paralogous sequence variants (PSVs) are short differences between homologous sequences within duplicated loci. It has been shown that many PSVs are not fixed in the population, which reduces their potential to differentiate paralogous regions. Moreover, segmental duplications exhibit extensive copy number variation, and are characterized by poor read mappability even for long-read data. All these factors lead to diminished accuracy of existing bioinformatical tools for short- and long-read data in duplicated regions. This dissertation presents three novel computational methods that solve classical bioinformatical problems (read mapping, variant calling and copy number variation detection) in LCR regions. In contrast to existing tools, three proposed methods examine PSV genotypes in order to distinguish sets of reliable and unreliable PSVs, and use reliable PSVs to achieve higher accuracy than state-of-the-art methods in the field.First, we describe a probabilistic method, DuploMap, designed to improve the accuracy of long-read mapping within LCR regions. It iteratively genotypes PSVs and leverages reliable PSVs to distinguish between candidate read locations. This allows for high accuracy variant calling in segmental duplications using long reads. Next, we present the first toolkit for LCR regions, Parascopy. Parascopy uses short-read whole-genome sequencing to estimate total copy number as well as paralog-specific copy number for duplicated genes. Parascopy analyzes reads mapped to different repeat copies and utilizes multiple samples to mitigate sequencing bias and identify reliable PSVs. Accurate copy number estimation facilitates discovery of pathogenic copy number changes in duplicated genes. A novel variant caller, ParascopyVC, builds upon copy number variation detection and uses short-read data to call pooled and locus-specific variants within segmental duplications. ParascopyVC uses population allele frequencies and pooled genotypes to select informative PSVs. Finally, the tool uses informative PSVs to identify additional locus-specific variants, enabling the discovery of novel disease-causing variants in duplicated genes
Locityper source code
No full text<p>Source code for Locityper (<a href="https://github.com/tprodanov/locityper">https://github.com/tprodanov/locityper</a>) and additional benchmarking scripts (<a href="https://github.com/tprodanov/locityper-bench">https://github.com/tprodanov/locityper-bench</a>).</p>
<p>Some scripts can also be found in <code>locityper/extra</code>.</p>
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Robust and accurate estimation of paralog-specific copy number for duplicated genes using whole-genome sequencing
Full text linkThe human genome contains hundreds of low-copy repeats (LCRs) that are challenging to analyze using short-read sequencing technologies due to extensive copy number variation and ambiguity in read mapping. Copy number and sequence variants in more than 150 duplicated genes that overlap LCRs have been implicated in monogenic and complex human diseases. We describe a computational tool, Parascopy, for estimating the aggregate and paralog-specific copy number of duplicated genes using whole-genome sequencing (WGS). Parascopy is an efficient method that jointly analyzes reads mapped to different repeat copies without the need for global realignment. It leverages multiple samples to mitigate sequencing bias and to identify reliable paralogous sequence variants (PSVs) that differentiate repeat copies. Analysis of WGS data for 2504 individuals from diverse populations showed that Parascopy is robust to sequencing bias, has higher accuracy compared to existing methods and enables prioritization of pathogenic copy number changes in duplicated genes
Recommended from our members
Sensitive alignment using paralogous sequence variants improves long-read mapping and variant calling in segmental duplications
Full text linkThe ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long-read mapping in segmental duplications. It analyzes reads mapped to segmental duplications using existing long-read aligners and leverages paralogous sequence variants (PSVs)-sequence differences between paralogous sequences-to distinguish between multiple alignment locations. On simulated datasets, DuploMap increased the percentage of correctly mapped reads with high confidence for multiple long-read aligners including Minimap2 (74.3-90.6%) and BLASR (82.9-90.7%) while maintaining high precision. Across multiple whole-genome long-read datasets, DuploMap aligned an additional 8-21% of the reads in segmental duplications with high confidence relative to Minimap2. Using DuploMap-aligned PacBio circular consensus sequencing reads, an additional 8.9 Mb of DNA sequence was mappable, variant calling achieved a higher F1 score and 14 713 additional variants supported by linked-read data were identified. Finally, we demonstrate that a significant fraction of PSVs in segmental duplications overlaps with variants and adversely impacts short-read variant calling
Sensitive alignment using paralogous sequence variants improves long-read mapping and variant calling in segmental duplications
No full text- …
