Pathogenic germline variants in 10,389 adult cancers
We conducted the largest investigation of predisposition variants in cancer to date,
discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 …
discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 …
Objective assessment of the evolutionary action equation for the fitness effect of missense mutations across CAGI‐blinded contests
P Katsonis, O Lichtarge - Human mutation, 2017 - Wiley Online Library
A major challenge in genome interpretation is to estimate the fitness effect of coding variants
of unknown significance (VUS). Labor, limited understanding of protein functions, and lack of …
of unknown significance (VUS). Labor, limited understanding of protein functions, and lack of …
Comprehensive genomic characterization of parathyroid cancer identifies novel candidate driver mutations and core pathways
Context Elucidating the genomic landscape of sporadic parathyroid carcinoma (PC) has
been limited by low tumor incidence. Objective Identify driver mutations of sporadic PC and …
been limited by low tumor incidence. Objective Identify driver mutations of sporadic PC and …
A method to delineate de novo missense variants across pathways prioritizes genes linked to autism
Genotype-phenotype relationships shape health and population fitness but remain difficult to
predict and interpret. Here, we apply an evolutionary action method to de novo missense …
predict and interpret. Here, we apply an evolutionary action method to de novo missense …
CAGI5: Objective performance assessments of predictions based on the Evolutionary Action equation
P Katsonis, O Lichtarge - Human mutation, 2019 - Wiley Online Library
Many computational approaches estimate the effect of coding variants, but their predictions
often disagree with each other. These contradictions confound users and raise questions …
often disagree with each other. These contradictions confound users and raise questions …
Germline genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes
There is an ongoing debate on the importance of genetic factors in cancer development,
where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer …
where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer …
Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease
The strongest genetic risk factor for idiopathic late‐onset Alzheimer's disease (LOAD) is
apolipoprotein E (APOE) ɛ4, while the APOE ɛ2 allele is protective. However, there are …
apolipoprotein E (APOE) ɛ4, while the APOE ɛ2 allele is protective. However, there are …
A comprehensive analysis of clinical and polygenic germline influences on somatic mutational burden
Tumor mutational burden (TMB), the total number of somatic mutations in the tumor, and
copy number burden (CNB), the corresponding measure of aneuploidy, are established …
copy number burden (CNB), the corresponding measure of aneuploidy, are established …
Substantial batch effects in TCGA exome sequences undermine pan-cancer analysis of germline variants
Background In recent years, research on cancer predisposition germline variants has
emerged as a prominent field. The identity of somatic mutations is based on a reliable …
emerged as a prominent field. The identity of somatic mutations is based on a reliable …
Methods to enhance the reproducibility of precision medicine
During January 2015, President Obama announced the Precision Medicine Initiative [1],
strengthening communal efforts to integrate patient-centric molecular, environmental, and …
strengthening communal efforts to integrate patient-centric molecular, environmental, and …