Christopher A. Cassa
Brigham and Women's Hospital
Data miningDiseaseGeneticsMedicineBiology
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Publications 39
#1Sahar NissimH-Index: 13
#2Ignaty Leshchiner (Broad Institute)H-Index: 20
Last. Wolfram GoesslingH-Index: 34
view all 33 authors...
Pancreatic ductal adenocarcinoma is an aggressive cancer with limited treatment options1. Approximately 10% of cases exhibit familial predisposition, but causative genes are not known in most families2. We perform whole-genome sequence analysis in a family with multiple cases of pancreatic ductal adenocarcinoma and identify a germline truncating mutation in the member of the RAS oncogene family-like 3 (RABL3) gene. Heterozygous rabl3 mutant zebrafish show increased susceptibility to cancer forma...
1 CitationsSource
#1Anwoy Kumar Mohanty (Brigham and Women's Hospital)H-Index: 2
#2Dana Vuzman (Brigham and Women's Hospital)H-Index: 13
Last. Shamil R. Sunyaev (Harvard University)H-Index: 67
view all 6 authors...
#1Max W. Shen (MIT: Massachusetts Institute of Technology)H-Index: 6
#2Mandana Arbab (Broad Institute)H-Index: 4
Last. Richard I. Sherwood (Brigham and Women's Hospital)H-Index: 22
view all 10 authors...
In this Article, a data processing error affected Fig. 3e and Extended Data Table 2; these errors have been corrected online.
1 CitationsSource
#1Christopher A. Cassa (Broad Institute)H-Index: 18
#2Donate Weghorn (Harvard University)H-Index: 3
Last. Shamil R. Sunyaev (Broad Institute)H-Index: 67
view all 11 authors...
1 CitationsSource
#1Max W. Shen (MIT: Massachusetts Institute of Technology)H-Index: 6
#2Mandana Arbab (Broad Institute)H-Index: 4
Last. Richard I. Sherwood (Brigham and Women's Hospital)H-Index: 22
view all 10 authors...
Following Cas9 cleavage, DNA repair without a donor template is generally considered stochastic, heterogeneous and impractical beyond gene disruption. Here, we show that template-free Cas9 editing is predictable and capable of precise repair to a predicted genotype, enabling correction of disease-associated mutations in humans. We constructed a library of 2,000 Cas9 guide RNAs paired with DNA target sites and trained inDelphi, a machine learning model that predicts genotypes and frequencies of 1...
48 CitationsSource
#1Donate Weghorn (Harvard University)H-Index: 3
#2Daniel J. Balick (Harvard University)H-Index: 7
Last. Shamil R. Sunyaev (Harvard University)H-Index: 67
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The fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of P...
3 CitationsSource
#1Christopher A. Cassa (Harvard University)H-Index: 18
#2Daniel M. Jordan (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 13
Last. Shamil R. Sunyaev (Harvard University)H-Index: 67
view all 4 authors...
Over 150,000 variants have been reported to cause Mendelian disease in the medical literature. It is still difficult to leverage this knowledge base in clinical practice, as many reports lack strong statistical evidence or may include false associations. Clinical laboratories assess whether these variants (along with newly observed variants that are adjacent to these published ones) underlie clinical disorders. We investigated whether citation data—including journal impact factor and the number ...
#1Alireza HaghighiH-Index: 9
#4Joel B. Krier (Brigham and Women's Hospital)H-Index: 14
Last. Dana Vuzman (Broad Institute)H-Index: 13
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Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/W...
7 CitationsSource
#1Maria Kousi (Duke University)H-Index: 17
#2O Söylemez (Broad Institute)H-Index: 1
Last. Nicholas Katsanis (Duke University)H-Index: 79
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The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remains unclear. We performed a systematic secondary-variant burden analysis of two independent Bardet-Biedl syndrome (BBS) cohorts with known recessive biallelic pathogenic mutations in one of 17 BBS genes for each individual. We observed a significant enrichment of trans-acting rare nonsynonymous secondary variants compared to either populat...
2 CitationsSource
#1Judith R. KelsenH-Index: 16
#2Jodie OuahedH-Index: 7
Last. Claudio G. GiraudoH-Index: 18
view all 32 authors...
1 CitationsSource