Pathway discovery by genome-wide, high-throughput, quantitative mass spectrometry

Genome-wide high-throughput mass spectrometry has emerged as an important new source of data on biological systems. This technology yields global information about the proteins expressed by an organism; consequently, biological processes can be studied without prior assumptions about the proteins that are involved. A profile of up- and down-regulated proteins is obtained which can be used to discover the gene-expression and cellular signaling pathways that underlie disease states and/or responses to treatments. Many data-manipulation steps are involved in obtaining pathway information from mass spectrometry of protease-digested complex mixtures of proteins. In this paper, we describe work to create a seamless data flow through these steps from peptide detection to queries of pathway databases based on patterns of up- and down-regulated proteins. Data from a mouse-model study of chronic obstructive pulmonary disease (COPD) are used to illustrate our results.