User profiles for Jack Kosmicki

Jack A. Kosmicki

Regeneron Genetics Center
Verified email at fas.harvard.edu
Cited by 31433

[HTML][HTML] Analysis of protein-coding genetic variation in 60,706 humans

…, T Tukiainen, DP Birnbaum, JA Kosmicki… - Nature, 2016 - nature.com
Large-scale reference data sets of human genetic variation are critical for the medical and
functional interpretation of DNA sequence changes. Here we describe the aggregation and …

[HTML][HTML] The mutational constraint spectrum quantified from variation in 141,456 humans

…, M Singer-Berk, EM England, EG Seaby, JA Kosmicki… - Nature, 2020 - nature.com
Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes that are crucial for the function …

Synaptic, transcriptional and chromatin genes disrupted in autism

…, L Liu, M Fromer, S Walker, T Singh, L Klei, J Kosmicki… - Nature, 2014 - nature.com
The genetic architecture of autism spectrum disorder involves the interplay of common and
rare variants and their impact on hundreds of genes. Using exome sequencing, here we …

[PDF][PDF] Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

FK Satterstrom, JA Kosmicki, J Wang, MS Breen… - Cell, 2020 - cell.com
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n
= 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to …

[HTML][HTML] Exome sequencing and analysis of 454,787 UK Biobank participants

…, E Maxwell, L Gurski, K Watanabe, JA Kosmicki… - Nature, 2021 - nature.com
A major goal in human genetics is to use natural variation to understand the phenotypic
consequences of altering each protein-coding gene in the genome. Here we used exome …

[PDF][PDF] Predicting splicing from primary sequence with deep learning

…, SF Darbandi, D Knowles, YI Li, JA Kosmicki… - Cell, 2019 - cell.com
The splicing of pre-mRNAs into mature transcripts is remarkable for its precision, but the
mechanisms by which the cellular machinery achieves such specificity are incompletely …

Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes

…, M Singer-Berk, EM England, EG Seaby, JA Kosmicki… - biorxiv, 2019 - biorxiv.org
Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes critical for an organism’s …

A framework for the interpretation of de novo mutation in human disease

…, C Stevens, A Sabo, LM McGrath, JA Kosmicki… - Nature …, 2014 - nature.com
Spontaneously arising (de novo) mutations have an important role in medical genetics. For
diseases with extensive locus heterogeneity, such as autism spectrum disorders (ASDs), the …

[HTML][HTML] Computationally efficient whole-genome regression for quantitative and binary traits

…, L Barnard, J Backman, A Marcketta, JA Kosmicki… - Nature …, 2021 - nature.com
Genome-wide association analysis of cohorts with thousands of phenotypes is computationally
expensive, particularly when accounting for sample relatedness or population structure. …

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

…, EM Wigdor, S Ripke, RK Walters, JA Kosmicki… - Nature …, 2017 - nature.com
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation.
We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of …