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Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
Onco-proteogenomics: cancer proteomics joins forces with genomics
Javier A Alfaro1, Ankit Sinha2, Thomas Kislinger2
11] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [2] Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. [3] Informatics &Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Abstract:
The complexities of tumor genomes are rapidly being uncovered, but how they are regulated into functional proteomes remains poorly understood. Standard proteomics workflows use databases of known proteins, but these databases do not capture the uniqueness of the cancer transcriptome, with its point mutations, unusual splice variants and gene fusions. Onco-proteogenomics integrates mass spectrometry-generated data with genomic information to identify tumor-specific peptides. Linking tumor-derived DNA, RNA and protein measurements into a central-dogma perspective has the potential to improve our understanding of cancer biology.
Insights
Onco-proteogenomics integrates genomic data with mass spectrometry to identify unique cancer peptides. This approach enhances understanding of cancer biology by linking DNA, RNA, and protein measurements.
Area of Science:
- Oncology
- Proteomics
- Genomics
Background:
- Tumor genome complexity is increasingly understood, yet proteome regulation remains unclear.
- Standard proteomics relies on known protein databases, missing cancer-specific transcriptome variations like mutations, splice variants, and gene fusions.
Purpose of the Study:
- To introduce and explain the concept of onco-proteogenomics.
- To highlight the limitations of current proteomics in capturing cancer-specific proteomic profiles.
- To propose an integrated approach for a comprehensive understanding of cancer biology.
Main Methods:
- Onco-proteogenomics integrates mass spectrometry data with genomic information.
- This approach identifies tumor-specific peptides by analyzing cancer transcriptomes.
- It links measurements from tumor-derived DNA, RNA, and proteins.
Main Results:
- Standard proteomics workflows fail to capture unique cancer peptides arising from mutations and alternative splicing.
- Onco-proteogenomics enables the identification of these tumor-specific peptides.
- The integration of multi-omics data provides a more complete picture of the cancer proteome.
Conclusions:
- Onco-proteogenomics offers a powerful strategy to bridge the gap between cancer genomics and proteomics.
- Linking DNA, RNA, and protein data is crucial for a deeper understanding of cancer biology.
- This integrated approach has the potential to uncover novel cancer mechanisms and therapeutic targets.
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