PT  - JOURNAL ARTICLE
AU  - Nathaniel Kwok
AU  - Zita Aretz
AU  - Sumiko Takao
AU  - Zheng Ser
AU  - Paolo Cifani
AU  - Alex Kentsis
TI  - Integrative proteogenomics using ProteomeGenerator2
AID  - 10.1101/2023.01.04.522774
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.04.522774
4099  - http://biorxiv.org/content/early/2023/01/04/2023.01.04.522774.short
4100  - http://biorxiv.org/content/early/2023/01/04/2023.01.04.522774.full
AB  - Recent advances in nucleic acid sequencing now permit rapid and genome-scale analysis of genetic variation and transcription, enabling population-scale studies of human biology, disease, and diverse organisms. Likewise, advances in mass spectrometry proteomics now permit highly sensitive and accurate studies of protein expression at the whole proteome-scale. However, most proteomic studies rely on consensus databases to match spectra to peptide and proteins sequences, and thus remain limited to the analysis of canonical protein sequences. Here, we develop ProteomeGenerator2 (PG2), based on the scalable and modular ProteomeGenerator framework. PG2 integrates genome and transcriptome sequencing to incorporate protein variants containing amino acid substitutions, insertions, and deletions, as well as non-canonical reading frames, exons, and other variants caused by genomic and transcriptomic variation. We benchmarked PG2 using synthetic data and genomic, transcriptomic, and proteomic analysis of human leukemia cells. PG2 can be integrated with current and emerging sequencing technologies, assemblers, variant callers, and mass spectral analysis algorithms, and is available open-source from https://github.com/kentsisresearchgroup/ProteomeGenerator2.Competing Interest StatementThe authors have declared no competing interest.