Mass spectrometry-based protein identification with accurate statistical significance assignment.

ABSTRACT:

Motivation

Assigning statistical significance accurately has become increasingly important as metadata of many types, often assembled in hierarchies, are constructed and combined for further biological analyses. Statistical inaccuracy of metadata at any level may propagate to downstream analyses, undermining the validity of scientific conclusions thus drawn. From the perspective of mass spectrometry-based proteomics, even though accurate statistics for peptide identification can now be achieved, accurate protein level statistics remain challenging.

Results

We have constructed a protein ID method that combines peptide evidences of a candidate protein based on a rigorous formula derived earlier; in this formula the database P-value of every peptide is weighted, prior to the final combination, according to the number of proteins it maps to. We have also shown that this protein ID method provides accurate protein level E-value, eliminating the need of using empirical post-processing methods for type-I error control. Using a known protein mixture, we find that this protein ID method, when combined with the Sori? formula, yields accurate values for the proportion of false discoveries. In terms of retrieval efficacy, the results from our method are comparable with other methods tested.

Availability and implementation

The source code, implemented in C++ on a linux system, is available for download at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbp/qmbp_ms/RAId/RAId_Linux_64Bit.

SUBMITTER: Alves G 

PROVIDER: S-EPMC4341067 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature