My personal mutanome: a computational genomic medicine platform for searching network perturbing alleles linking genotype to phenotype

Yadi Zhou; Junfei Zhao; Jiansong Fang; William Martin; Lang Li; Ruth Nussinov; Timothy A Chan; Charis Eng; Feixiong Cheng

doi:10.1186/s13059-021-02269-3

My personal mutanome: a computational genomic medicine platform for searching network perturbing alleles linking genotype to phenotype

Genome Biol. 2021 Jan 29;22(1):53. doi: 10.1186/s13059-021-02269-3.

Authors

Yadi Zhou^#¹, Junfei Zhao^#^{2

3}, Jiansong Fang^#¹, William Martin¹, Lang Li⁴, Ruth Nussinov^{5

6}, Timothy A Chan^{1

7

8

9

10}, Charis Eng^{1

8

9

10

11}, Feixiong Cheng^{12

13

14}

Affiliations

¹ Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
² Department of Systems Biology, Herbert Irving Comprehensive Center, Columbia University, New York, NY, 10032, USA.
³ Department of Biomedical Informatics, Columbia University, New York, NY, 10032, USA.
⁴ Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.
⁵ Computational Structural Biology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, 21702, USA.
⁶ Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
⁷ Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
⁸ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
⁹ Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
¹⁰ Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
¹¹ Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
¹² Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. chengf@ccf.org.
¹³ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA. chengf@ccf.org.
¹⁴ Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. chengf@ccf.org.

^# Contributed equally.

Abstract

Massive genome sequencing data have inspired new challenges in personalized treatments and facilitated oncological drug discovery. We present a comprehensive database, My Personal Mutanome (MPM), for accelerating the development of precision cancer medicine protocols. MPM contains 490,245 mutations from over 10,800 tumor exomes across 33 cancer types in The Cancer Genome Atlas mapped to 94,563 structure-resolved/predicted protein-protein interaction interfaces ("edgetic") and 311,022 functional sites ("nodetic"), including ligand-protein binding sites and 8 types of protein posttranslational modifications. In total, 8884 survival results and 1,271,132 drug responses are obtained for these mapped interactions. MPM is available at https://mutanome.lerner.ccf.org .

Keywords: Edgetic; Mutanome; Nodetic; Precision cancer medicine; Protein-protein interaction; Somatic mutations.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles*
Computational Biology
Drug Discovery
Exome
Genomics*
Genotype*
Humans
Mutation
Neoplasms / genetics*
Phenotype*
Protein Interaction Domains and Motifs
Protein Processing, Post-Translational

Abstract

Publication types

MeSH terms

Grants and funding