# Center of Excellence for High Throughput Proteogenomic Characterization

> **NIH NIH U24** · BROAD INSTITUTE, INC. · 2020 · $1,286,216

## Abstract

Project Summary (Carr, Mertins)
Genetic alterations in human cancer have been systematically mapped by genomics landscape
studies in the past decade, however, the direct consequences of these alterations on the
functional proteome are poorly understood. Deep scale, mass spectrometry-based proteomic
studies of three tumor types in the current phase of the Clinical Proteomics Tumor Analysis
Consortium (CPTAC) program have revealed that integration of proteomic data with genomic
data can improve specificity for identifying cancer-relevant pathways triggered by somatic DNA
variants or DNA copy number alterations (CNAs) compared to genomic characterization alone,
and help narrow target selection for potential therapeutic intervention. Here we propose to
extend proteogenomic characterization to additional genetically defined tumor types – lung,
brain and pancreatic cancer – and preclinical patient-derived tumor xenografts and cell line
models. State-of-the-art LC-MS/MS proteomics technology with highly multiplexed stable-
isotope mass tagging (TMT 10-plex) will be employed for precise relative quantification of the
proteome, phosphoproteome and acetylome with very deep coverage. Improved multiplexing
capabilities in these discovery type analyses enable a throughput of over 500 samples per year
in conjunction with longitudinal quality control performance measurements. The proteome data
produced will be integrated with genomics data in collaboration with the CPTAC
Proteogenomics Data Analysis Centers. The goal will be to identify proteins with somatic
variants or cancer-specific splice site junctions, correlate effects between copy number
alterations and protein expression, and to identify signaling pathways in the phosphoproteome
and lysine-acetylome that are activated by genetic alterations. This proteogenomics approach
will inform target selection for confirmatory targeted mass spectrometry assays with a particular
emphasis on mutated proteins, oncogenic regulators/effectors, and druggable proteins. We will
develop and deploy new and existing analytically validated, highly multiplexed targeted MS-
based assays (MRM and PRM) to measure cancer-relevant proteins and modified peptides in
human biospecimens for candidate verification. Stable isotope-labeled peptides will be used as
internal standards for unambiguous identification and quantification at a multiplex level of up to
200 analytes per assay. Existing technology will be further developed to enable comprehensive
analysis of rare tumor cell populations, to evaluate tumor heterogeneity, to increase depth and
breadth of post-translational modification analysis, and to improve depth, reliability and
repeatability of peptide i.d. and quantification in general by intelligent data acquisition.

## Key facts

- **NIH application ID:** 10001970
- **Project number:** 5U24CA210986-05
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** STEVEN A CARR
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,286,216
- **Award type:** 5
- **Project period:** 2016-09-14 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001970

## Citation

> US National Institutes of Health, RePORTER application 10001970, Center of Excellence for High Throughput Proteogenomic Characterization (5U24CA210986-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001970. Licensed CC0.

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