The Cancer Proteome Atlas (TCPA) Project based on Mass Spectrometry

Label-free mass spectrometry based on Data Independent Acquisition (DIA) is high-throughput and reproducible, opening up the opportunity for a multi-laboratory collaborative cancer proteome profiling effort, a la TCGA, The Cancer Proteome Atlas (TCPA). This DIA-MS based TCPA is complementary to the on-going antibody-based TCPA developed by MD Anderson and the deep proteogenomics profiling of the Clinical Proteomic Tumor Analysis Consortium (CPTAC).

The global aims of TCPA based on Mass Spectrometry analysis are

1. to better understand the molecular underpinnings of cancer.
2. to identify core and cancer type enriched molecular therapeutic targets and biomarkers.

As a first step, Guo and Jimenez recently described a mass spectrometric pipeline and spectral resource to support DIA-based biomarker studies and reported a comprehensive DIA pan-human library from 1,096 data dependent acquisition MS raw files, comprising 242,476 unique peptide sequences from 14,782 protein groups and 10,943 SwissProt-annotated proteins expressed in 16 types of cancer samples (publication).

Underscoring the high potential of DIA-MS for TCPA, a collaborative study led by Yue Xuan (Thermo Fisher) showed that harmonized MS instrument platforms and standardized data acquisition procedures demonstrated robust, sensitive, and reproducible data generation across eleven sites in nine countries on seven consecutive days in a 24/7 operation mode (publication).

A first draft proteome of over 999 tumors representing 22 cancer types was presented at HUPO Cancun in 2022. The study has been submitted for publication. The pan-cancer proteome landscape will be queriable and downloadable via the R2 data analysis platform hosted at Amsterdam UMC.