Document text
Principal Investigator: Rachel Karchin
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $633,077
Funding agency: National Cancer Institute
PROJECT SUMMARY
Cancer sequencing projects have identified a very large number of DNA mutations whose importance in cancer
is not yet understood. To better understand the impact of these mutations, our team has produced a software
tool for computational analysis of cancer mutations that can analyze millions of mutations at one time. This tool
works as a funnel to help researchers to find the small number of mutations that are most likely to be informative
from the very large number of mutations discovered in a sequencing project. The software allows users to design
ways to combine multiple mutation evaluation metrics, and generate a prioritized list of mutations that are more
likely to be biologically important. These evaluation metrics include the molecular consequence, bioinformatic
scores to identify pathogenic and driver mutations, frequency of the mutation in human populations, previous
occurrence in tumor tissue types, pointers to literature, and visualization of annotated protein structures and
networks. A web-based version of the pipeline - Cancer Related Analysis of Variants Toolkit (CRAVAT) has been
widely adopted (3000+ jobs submitted/month on average in 2020). We have attracted a user community that
spans both basic and clinical cancer researchers, all of whom rely on high-throughput tumor sequencing in their
work. In 2019, we introduced OpenCRAVAT, which is distinguished by an open source codebase and an open
app store of tools and resources that can be used to better understand the importance and impact of mutations.
The app store is driven by the user community; new apps are prioritized based upon user requests and the app
store includes many apps that were contributed directly by outside tool developers. The app store currently
aggregates tools from over 70 organizations, and these tools can be combined to identify mutations whose
molecular impact contributes to tumorigenesis, prognosis and treatment selection. Initial adoption of our
OpenCRAVAT tool is encouraging, with over 10,000 local package downloads in the first two years. We expect
that OpenCRAVAT will be adopted by a much larger community, given the increasing importance of DNA
sequencing data in cancer research. We will continue to ensure that our tools are interoperable with other
informatics tools and services, and can be run in different computational environments such as cloud computing
and local installation to maintain data privacy.
Terms: <Address><Adopted><Adoption><Allele Frequency><Antigenic Determinants><Architecture><Binding Determinants><Bio-Informatics><Bioinformatics><Cancer Patient><Cancers><Characteristics><Clinical><Cloud Computing><Cloud Infrastructure><Cloud Service><Collaborations><Collection><Communities><Complex><Computational toolkit><Computer Analysis><Computer Software Tools><Computer software><Custom><DNA Alteration><DNA Sequence><DNA Sequence Alteration><DNA mutation><DNA seq><DNA sequencing><DNAseq><Data><Data Bases><Data Commons><Data Set><Databases><Disease><Disorder><Educational workshop><Engineering / Architecture><Ensure><Environment><Epitopes><Evaluation><Feedback><Frequencies><Friends><Functional RNA><Gene Frequency><Gene variant><Generalized Growth><Genes><Genetic Alteration><Genetic Change><Genetic defect><Genetic mutation><Genomics><Germ-Line Mutation><Germline Mutation><Graphical interface><Growth><Haplotypes><Hereditary Mutation><Human><Individual><Investigators><Investments><Jobs><Language><Literature><Malignant Neoplasms><Malignant Tumor><Measures><Modern Man><Molecular><Mutation><Non-Coding><Non-Coding RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Occupations><On-Line Systems><Oncogenesis><Online Systems><Pathogenicity><Population><Professional Positions><Prognosis><Property><Recurrence><Recurrent><Research Personnel><Research Resources><Researchers><Resources><Running><Sampling><Selection for Treatments><Sequence Alteration><Services><Side><Software><Software Tools><Somatic Mutation><Source><Source Code><Subgroup><System><Techniques><Time><Tissue Growth><Training><Tumor Tissue><Untranslated RNA><Update><Variant><Variation><Visualization><Visualization software><Work><Workshop><allele variant><allelic frequency><allelic variant><anti-cancer research><base><bases><cancer genomics><cancer research><cancer sub-types><cancer subtypes><cloud based computing><cloud computer><cloud platform><cloud server><cohort><computational analyses><computational analysis><computational toolbox><computational tools><computational toolset><computer analyses><computerized tools><conference><convention><customs><data base><data privacy><design><designing><driver lesion><driver mutation><flexibility><flexible><genetic variant><genome mutation><genomic alteration><genomic variant><genomics cloud><germ-line defect><germline variant><graphic user interface><graphical user interface><hack day><hackathon><hackfest><high throughput analysis><improved><in silico><informatics tool><interoperability><malignancy><meeting><meetings><neoplasm/cancer><noncoding><oncogenomics><online computer><ontogeny><open source><outreach><parallel processing><patient subclass><patient subcluster><patient subgroups><patient subpopulations><patient subsets><patient subtypes><protein structure><protein structures><proteins structure><recruit><selection of treatment><skills><social media><software toolkit><software user interface><somatic variant><success><summit><symposia><symposium><task analysis><therapy selection><tool><treatment selection><tumor><tumorigenesis><usability><visualization tool><web based><web server><web tool><web-based tool>