DART-ID increases single-cell proteome coverage


Chen AT, Franks A, Slavov N. DART-ID increases single-cell proteome coverage. PLOS Computational Biology [Internet]. 2019;15 (7) :1-30.

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Author summary Identifying and quantifying proteins in single cells gives researchers the ability to tackle complex biological problems that involve single cell heterogeneity, such as the treatment of solid tumors. Mass spectrometry analysis of peptides can identify their sequence from their masses and the masses of their fragment ion, but often times these pieces of evidence are insufficient for a confident peptide identification. This problem is exacerbated when analyzing lowly abundant samples such as single cells. To identify even peptides with weak mass spectra, DART-ID incorporates their retention time—the time when they elute from the liquid chromatography used to physically separate them. We present both a novel method of aligning the retention times of peptides across experiments, as well as a rigorous framework for using the estimated retention times to enhance peptide sequence identification. Incorporating the retention time as additional evidence leads to a substantial increase in the number of samples in which proteins are confidently identified and quantified.