My Cancer Genome: Coevolution of Precision Oncology and a Molecular Oncology Knowledgebase

Abstract

PURPOSE The My Cancer Genome (MCG) knowledgebase and resulting website were launched in 2011 with the purpose of guiding clinicians in the application of genomic testing results for treatment of patients with cancer. Both knowledgebase and website were originally developed using a wiki-style approach that relied on manual evidence curation and synthesis of that evidence into cancer-related biomarker, disease, and pathway pages on the website that summarized the literature for a clinical audience. This approach required significant time investment for each page, which limited website scalability as the field advanced. To address this challenge, we designed and used an assertion-based data model that allows the knowledgebase and website to expand with the field of precision oncology. METHODS Assertions, or computationally accessible cause and effect statements, are both manually curated from primary sources and imported from external databases and stored in a knowledge management system. To generate pages for the MCG website, reusable templates transform assertions into reconfigurable text and visualizations that form the building blocks for automatically updating disease, biomarker, drug, and clinical trial pages. RESULTS Combining text and graph templates with assertions in our knowledgebase allows generation of web pages that automatically update with our knowledgebase. Automated page generation empowers rapid scaling of the website as assertions with new biomarkers and drugs are added to the knowledgebase. This process has generated more than 9,100 clinical trial pages, 18,100 gene and alteration pages, 900 disease pages, and 2,700 drug pages to date. CONCLUSION Leveraging both computational and manual curation processes in combination with reusable templates empowers automation and scalability for both the MCG knowledgebase and MCG website.

Identification of neoepitope reactive T-cell receptors guided by HLA-A*03:01 and HLA-A*11:01 immunopeptidomics

“…We evaluated the processing and presentation of 10 common oncogene mutations that occur across multiple tumor types ( table 1 ). 40 41 Most mutations were cloned individually into separate retroviral ‘minigene’ vectors ( online supplemental table 1 ). The three EGFR mutations were cloned into the same retroviral construct as sequential mutated minigenes (referred to as ‘Trivalent Tandem Minigene’, or TMG) or sequential mutated exons (referred to as ‘Trivalent Tandem Exon’, or TE).…”

MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC

“…In previous study, we reported that the acquired high-frequency mutation of MRE11:p.K464R in ovarian cancer patients undergoing Olaparib maintenance therapy, and preliminarily elucidate its correlation with Olaparib resistance [ 17 ]. Moreover, we did not find the record of MRE11:p.K464R mutation by searching databases (Cosmic database [ 37 ], My Cancer Genome database [ 38 ], ICGC database ( http://icgc.org ), TCGA database ( http://www.cancer.gov/ccg/research/genome-sequencing/tcga )), which strongly suggests that acquired MRE11:p.K464R mutation may play a key role in causing Olaparib resistance and may be a specific biomarker for Olaparib and even PARP inhibitor resistance. Therefore, the exploration of the mechanism of resistance caused by MRE11:p.K464R mutation will expand the understanding of PARP inhibitor resistance, and is expected to provide new ideas for the formulation of combination therapy regimens after PARP inhibitor resistance.…”

Ku70 senses cytosolic DNA and assembles a tumor-suppressive signalosome

“…Data on the association between the expression of gene encoding Ku70 ( XRCC6 ) and survival of patients with colon and rectal adenocarcinoma were accessed from the Human Protein Atlas ( 115 ). The number of cancer cases with respect to alterations of XRCC6 and the type of alteration of XRCC6 was evaluated using the My Cancer Genome portal ( 116 ). Percentage copy number variation (amplification and deletion) in XRCC6 from patients with colon and rectal adenocarcinoma was evaluated using the Gene Set Cancer Analysis web server ( 117 ).…”