Artículos de revistas
Separating the wheat from the chaff: unbiased filtering of background tandem mass spectra improves protein identification
Fecha
2008Registro en:
JOURNAL OF PROTEOME RESEARCH, v.7, n.8, p.3382-3395, 2008
1535-3893
10.1021/pr800140v
Autor
JUNQUEIRA, Magno
SPIRIN, Victor
BALBUENA, Tiago Santana
WARIDEL, Patrice
SURENDRANATH, Vineeth
KRYUKOV, Grigoriy
ADZHUBEI, Ivan
THOMAS, Henrik
SUNYAEV, Shamil
SHEVCHENKO, Andrej
Institución
Resumen
Only a small fraction of spectra acquired in LC-MS/MS runs matches peptides from target proteins upon database searches. The remaining, operationally termed background, spectra originate from a variety of poorly controlled sources and affect the throughput and confidence of database searches. Here, we report an algorithm and its software implementation that rapidly removes background spectra, regardless of their precise origin. The method estimates the dissimilarity distance between screened MS/MS spectra and unannotated spectra from a partially redundant background library compiled from several control and blank runs. Filtering MS/MS queries enhanced the protein identification capacity when searches lacked spectrum to sequence matching specificity. In sequence-similarity searches it reduced by, on average, 30-fold the number of orphan hits, which were not explicitly related to background protein contaminants and required manual validation. Removing high quality background MS/MS spectra, while preserving in the data set the genuine spectra from target proteins, decreased the false positive rate of stringent database searches and improved the identification of low-abundance proteins.