The goals of the Bioinformatics, Biostatistics, and Image Analyses Core are to provide biostatistical and bioinformatics expertise and computational tools for genome-scale transcriptomic and epigenomic studies, as well as perform multiplex immunofluorescence profiling and analyses of tumor immune microenvironments. The work of the Core will ensure optimal study designs, quality control, and statistical analyses of data, as well as sophisticated integration of data across different datasets and animal species. Analyses of ChIP-seq and RNA- seq data will utilize state-of-the-art algorithms developed by a Core Co-Director. Multiplex immunofluorescence is coupled with quantitative digital image analysis using tissue and individual cell segmentation and cell phenotype analysis algorithms.
The specific aims of this Core are: 1) Support transcriptomic (RNA-seq) and epigenomic (ATAC-seq and ChIP- seq) analyses of cells and tumors upon gene and/or drug perturbation. 2) Support single-cell RNA-seq and T- cell receptor repertoire data analyses. 3) Support genetic screen data analyses and integration. 4) Conduct multiplex immunohistochemistry profiling and analyses. 5) Integrate data on cell lines and animal models with data from clinical samples and clinical trials. 6) Provide biostatistical and power analyses support. 7) Support data management and sharing among the different projects The rigorous computational tools and analyses provided by the Core will maximize confidence in validation of results and generation of new hypotheses toward the objective of overcoming resistance to targeted and immunotherapies for melanoma.

Public Health Relevance

The Bioinformatics, Biostatistics, and Image Analyses Core for the program project investigating epigenetic mechanisms of melanoma resistance to therapies will provide expertise and analysis tools to ensure that all experiments are soundly designed and appropriately analyzed. Epigenetic refers to factors in cells that change their behavior without changing gene sequences. The efforts of the Core will help ensure that drugs found to block factors driving resistance can be advanced toward clinical trials with confidence.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA163222-07
Application #
9989073
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2013-03-12
Project End
2024-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
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Nguyen, Nhu T; Fisher, David E (2018) MITF and UV responses in skin: From pigmentation to addiction. Pigment Cell Melanoma Res :
Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J et al. (2018) Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558:445-448
Romano, Gabriele; Chen, Pei-Ling; Song, Ping et al. (2018) A Preexisting Rare PIK3CAE545K Subpopulation Confers Clinical Resistance to MEK plus CDK4/6 Inhibition in NRAS Melanoma and Is Dependent on S6K1 Signaling. Cancer Discov 8:556-567
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Lin, William M; Fisher, David E (2017) Signaling and Immune Regulation in Melanoma Development and Responses to Therapy. Annu Rev Pathol 12:75-102
Kawakami, Akinori; Fisher, David E (2017) The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Invest 97:649-656
Reuben, Alexandre; Spencer, Christine N; Prieto, Peter A et al. (2017) Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med 2:

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