Phyloproteomics: what phylogenetic analysis reveals about serum proteomics

Abstract

Phyloproteomics is a novel analytical tool that solves the issue of comparability between proteomic analyses, utilizes a total spectrum-parsing algorithm, and produces biologically meaningful classification of specimens. Phyloproteomics employs two algorithms: a new parsing algorithm (UNIPAL) and a phylogenetic algorithm (MIX). By outgroup comparison, the parsing algorithm identifies novel or vanished MS peaks and peaks signifying up or down regulated proteins and scores them as derived or ancestral. The phylogenetic algorithm uses the latter scores to produce a biologically meaningful classification of the specimens.

Figure 1

Schematic representation of phyloproteomic analysis. The process involves two steps. The first is the algorithmic sorting of the m/z values into derived (exists in some but not all specimens) and ancestral (in all specimens); the derived values are those signifying either novel, vanished, or up and down regulated peaks. The second step is a parsimony phylogenetic analysis that groups the specimens on the basis of the shared derived values.

Figure 2

Phyloproteomic cladograms of three cancers: (A) pancreatic, (B) prostate, and (C) ovarian. The nodes of major clades are marked as follows: •, terminal cancer clade; ○, middle cancer clade; □, middle healthy clade; and ■, basal healthy clade. Transitional zones (TZ) are marked by bracketed arrows.

Figure 3

A phyloproteomic analysis showing dichotomous distribution of cancers into two clades. A schematic cladogram of a comprehensive phyloproteomic analysis composed of 460 specimens representing ovarian, pancreatic, and prostate cancers as well as noncancerous specimens. Specimens of every cancer type are classified into two clades: a terminal and middle, as well as transitional clades. Healthy specimens are classified into a major healthy clade and transitional clades.