Biology subjects

Layer, R. M.

Publications and source records attributed to Layer, R. M..

4 recordsLinked to original sources

bioRxiv2018

SV-plaudit: A cloud-based framework for manually curating thousands of structural variants

SV-plaudit is a framework for rapidly curating structural variant (SVs) predictions. For each SV, we generate an image that visualizes the coverage and alignment signals from a set of samples. Images are uploaded to our cloud framework where users assess the quality of each image using a client-side web application. Reports can then be generated as a tab-delimited file or annotated VCF. As a proof of principle, nine researchers collaborated for one hour to evaluate 1,350 SVs each. We anticipate that SV-plaudit will become a standard step in variant calling pipelines and the crowd-sourced curation of other biological results.\n\nCode available at https://github.com/jbelyeu/SV-plaudit\n\nDemonstration video available at https://www.youtube.com/watch?v=ono8kHMKxDs

bioinformatics↗

bioRxiv2017

A map of constrained coding regions in the human genome.

Deep catalogs of genetic variation collected from many thousands of humans enable the detection of intraspecies constraint by revealing coding regions with a scarcity of variation. While existing techniques summarize constraint for entire genes, single metrics cannot capture the fine-scale variability in constraint within each protein-coding gene. To provide greater resolution, we have created a detailed map of constrained coding regions (CCRs) in the human genome by leveraging coding variation observed among 123,136 humans from the Genome Aggregation Database (gnomAD). The most constrained coding regions in our map are enriched for both pathogenic variants in ClinVar and de novo mutations underlying developmental disorders. CCRs also reveal protein domain families under high constraint, suggest unannotated or incomplete protein domains, and facilitate the prioritization of previously unseen variation in studies of disease. Finally, a subset of CCRs with the highest constraint likely exist within genes that cause yet unobserved human phenotypes owing to strong purifying selection.

genomics↗

bioRxiv2017

GIGGLE: a search engine for large-scale integrated genome analysis

GIGGLE is a genomics search engine that identifies and ranks the significance of shared genomic loci between query features and thousands of genome interval files. GIGGLE scales to billions of intervals, is faster (+1,000X) than existing methods, and its speed extends the accessibility and utility of resources such as ENCODE, Roadmap Epigenomics, and GTEX by facilitating data integration and hypothesis generation. GIGGLE is available at https://github.com/ryanlayer/giggle.

bioinformatics↗

bioRxiv2017

Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families

Genomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across the size and frequency spectrum through whole genome sequencing of 519 ASD cases, their unaffected sibling controls, and parents. Cases carry a small excess of de novo (1.02-fold) noncoding variants, which is not significant after correcting for paternal age. Assessing 51,801 regulatory classes, no category is significantly associated with ASD after correction for multiple testing. The strongest signals are observed in coding regions, including structural variation not detected by previous technologies and missense variation. While rare noncoding variation likely contributes to risk in neurodevelopmental disorders, no category of variation has impact equivalent to loss-of-function mutations. Average effect sizes are likely to be smaller than that for coding variation, requiring substantially larger samples to quantify this risk.

genomics↗