Shotgun proteomics is the most commonly used technique for understanding the proteome of complex human samples. There is terabytes of proteomics data available on NCI's proteomics cloud, but unfortunately most proteomics search engine search a canonical human sequence database along with a handful of PTMs. Thus more than 50% of the MS/MS spectra remain uninterpreted. We have developed a cloud-based algorithm, Bolt, that can search almost more than 2.4 million protein sequences (canonical, isoforms and mutations) along with 41 PTMs and partial tryptic search in a matter of minutes. Bolt is able to search this 50 times larger search space in minutes whereas the traditional search engine need much longer even on a smaller search space. Utilizing the power of cloud computing, we are able to sequence 20% more MS/MS than traditional search engines. We propose adapting and integrating Bolt to the NCI's cloud platform, and linking it to the CRDC proteomics pipeline (for shotgun proteomics and neoantigen discovery) where scientists can analyse their existing and future data sets seamlessly while mining them much deeper than before. We also propose to link the genomic node to extract sample-specific information to futher mine proteogenomics data set for novel coding regions.
