Open-pFind enables precise, comprehensive and rapid peptide identification in shotgun proteomics

Chi, H.; Liu, C.; Yang, H.; Zeng, W.-F.; Wu, L.; Zhou, W.-J.; Niu, X.-N.; Ding, Y.-H.; Zhang, Y.; Wang, R.-M.; Wang, Z.-W.; Chen, Z.-L.; Sun, R.-X.; Liu, T.; Tan, G.-M.; Dong, M.-Q.; Xu, P.; Zhang, P.-H.; He, S.-M.

doi:10.1101/285395

bioRxiv · 10.1101/285395

Open-pFind enables precise, comprehensive and rapid peptide identification in shotgun proteomics

Chi, H.·Liu, C.·Yang, H.·Zeng, W.-F.·Wu, L.·Zhou, W.-J.·Niu, X.-N.·Ding, Y.-H.·Zhang, Y.·Wang, R.-M.·Wang, Z.-W.·Chen, Z.-L.·Sun, R.-X.·Liu, T.·Tan, G.-M.·Dong, M.-Q.·Xu, P.·Zhang, P.-H.·He, S.-M.

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Abstract

Shotgun proteomics has grown rapidly in recent decades, but a large fraction of tandem mass spectrometry (MS/MS) data in shotgun proteomics are not successfully identified. We have developed a novel database search algorithm, Open-pFind, to efficiently identify peptides even in an ultra-large search space which takes into account unexpected modifications, amino acid mutations, semi- or non-specific digestion and co-eluting peptides. Tested on two metabolically labeled MS/MS datasets, Open-pFind reported 50.5-117.0% more peptide-spectrum matches (PSMs) than the seven other advanced algorithms. More importantly, the Open-pFind results were more credible judged by the verification experiments using stable isotopic labeling. Tested on four additional large-scale datasets, 70-85% of the spectra were confidently identified, and high-quality spectra were nearly completely interpreted by Open-pFind. Further, Open-pFind was over 40 times faster than the other three open search algorithms and 2-3 times faster than three restricted search algorithms. Re-analysis of an entire human proteome dataset consisting of [~]25 million spectra using Open-pFind identified a total of 14,064 proteins encoded by 12,723 genes by requiring at least two uniquely identified peptides. In this search results, Open-pFind also excelled in an independent test for false positives based on the presence or absence of olfactory receptors. Thus, a practical use of the open search strategy has been realized by Open-pFind for the truly global-scale proteomics experiments of today and in the future.

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Chi, H., Liu, C., Yang, H., Zeng, W.-F., Wu, L., Zhou, W.-J., Niu, X.-N., Ding, Y.-H., Zhang, Y., Wang, R.-M., Wang, Z.-W., Chen, Z.-L., Sun, R.-X., Liu, T., Tan, G.-M., Dong, M.-Q., Xu, P., Zhang, P.-H., He, S.-M.. 2018-03-20. Open-pFind enables precise, comprehensive and rapid peptide identification in shotgun proteomics. https://doi.org/10.1101/285395

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