FIGURE 1.

Integrated network approach to uncover novel human autophagy effectors. A, Construction of protein interaction network centered on human proteins implicated in the core autophagy “machinery” (red squares) comprising the initiation factor (BECN1) and elongation components of the ATG12 conjugation system (ATG12, ATG7, ATG10, ATG5, and ATG16L1) and the LC3 conjugation cascade (MAP1LC3, ATG4, ATG7, and ATG3). Blues circles denote human proteins interacting with the core autophagy proteins. B, Yeast interolog projection. The human network is extended by projecting the yeast network centered on yeast autophagy proteins mapped to human orthologs. A more extensive figure of the yeast autophagy network is shown in supplemental Fig. S1A. C, The resulting hybrid yeast-human interaction map with orthologous interactions (or interologs) from the yeast network superimposed onto the human network. D, Combined with literature (PubMed) co-citation analysis, a number of components interacting with core ATG proteins derived from the hybrid map can be broadly annotated as having an involvement with membrane or vesicle structures. The intensity of the “heat map” denotes the extent to which each specific term is co-cited with each protein in the PubMed database.