Browsing by Subject "sequence alignment"

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Open Access
Div-blast: Diversification of sequence search results
(Public Library of Science, 2014) Eser, E.; Can, T.; Ferhatosmanoglu H.
Sequence similarity tools, such as BLAST, seek sequences most similar to a query from a database of sequences. They return results significantly similar to the query sequence and that are typically highly similar to each other. Most sequence analysis tasks in bioinformatics require an exploratory approach, where the initial results guide the user to new searches. However, diversity has not yet been considered an integral component of sequence search tools for this discipline. Some redundancy can be avoided by introducing non-redundancy during database construction, but it is not feasible to dynamically set a level of non-redundancy tailored to a query sequence. We introduce the problem of diverse search and browsing in sequence databases that produce non-redundant results optimized for any given query. We define diversity measures for sequences and propose methods to obtain diverse results extracted from current sequence similarity search tools. We also propose a new measure to evaluate the diversity of a set of sequences that is returned as a result of a sequence similarity query. We evaluate the effectiveness of the proposed methods in post-processing BLAST and PSIBLAST results. We also assess the functional diversity of the returned results based on available Gene Ontology annotations. Additionally, we include a comparison with a current redundancy elimination tool, CD-HIT. Our experiments show that the proposed methods are able to achieve more diverse yet significant result sets compared to static non-redundancy approaches. In both sequencebased and functional diversity evaluation, the proposed diversification methods significantly outperform original BLAST results and other baselines. A web based tool implementing the proposed methods, Div-BLAST, can be accessed at cedar.cs.bilkent.edu.tr/Div-BLAST © 2014 Eser et al.
Open Access
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder
(Elsevier, 2014) Dong, S.; Walker, M.F.; Carriero, N.J.; DiCola, M.; Willsey, A.; Ye, A.Y.; Waqar, Z.; Gonzalez L.E.; Overton J.D.; Frahm, S.; Keaney J.F.; III, Teran, N.A.; Dea J.; Mandell J.D.; HusBal V.; Sullivan, C.A.; DiLullo, N.M.; Khalil, R.O.; Gockley J.; Yuksel, Z.; Sertel, S.M.; Ercan-Sencicek, A.G.; Gupta, A.R.; Mane, S.M.; Sheldon, M.; Brooks, A.I.; Roeder, K.; Devlin, B.; State, M.W.; Wei L.; Sanders, S.J.
Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR= 1.6; 95% CI= 1.0-2.7; p= 0.03), are more common in female probands (p= 0.02), are enriched among genes encoding FMRP targets (p= 6× 10-9), and arise predominantly on the paternal chromosome (p< 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. © 2014 The Authors.