Kertesz-Farkas, A.; Acquaye, F. L. N. A.; Ostapenko, V.; Locon, R. H.; Lu, Y.; Grant, C. E.; Noble, W. S.

Over the past 30 years, software for searching tandem mass spectrometry data against a protein database has improved dramatically in speed and statistical power. However, existing tools can still struggle to analyze truly massive datasets, when either the number of spectra or the number of proteins being analyzed grows too large. Here we describe enhancements to the Tide search engine that allow it to handle datasets containing >10 million spectra and databases containing >7 billion peptides on commodity hardware. We demonstrate that the new Tide architecture is around 2-7 times faster than the previous version and is now comparable to MSFragger and Sage in speed while requiring much less memory. Tide is open source and is publicly available as pre-compiled binaries for Windows, Linux and Mac.