Text-based analysis of genes, proteins, aging, and cancer

Abstract The diverse nature of cancer- and aging-related genes presents a challenge for large-scale studies based on molecular sequence and profiling data. An underexplored source of data for modeling and analysis is the textual descriptions and annotations present in curated gene-centered biomedical corpora. Here, 450 genes designated by surveys of the scientific literature as being associated with cancer and aging were analyzed using two complementary approaches. The first, ensemble attribute profile clustering, is a recently formulated, text-based, semi-automated data interpretation strategy that exploits ideas from statistical information retrieval to discover and characterize groups of genes with common structural and functional properties. Groups of genes with shared and unique Gene Ontology terms and protein domains were defined and examined. Human homologs of a group of known Drosphila aging-related genes are candidates for genes that may influence lifespan ( hep /MAPK2K7, bsk /MAPK8, puc /LOC285193). These JNK pathway-associated proteins may specify a molecular hub that coordinates and integrates multiple intra- and extracellular processes via space- and time-dependent interactions with proteins in other pathways. The second approach, a qualitative examination of the chromosomal locations of 311 human cancer- and aging-related genes, provides anecdotal evidence for a “phenotype position effect”: genes that are proximal in the linear genome often encode proteins involved in the same phenomenon. Comparative genomics was employed to enhance understanding of several genes, including open reading frames, identified as new candidates for genes with roles in aging or cancer. Overall, the results highlight fundamental molecular and mechanistic connections between progenitor/stem cell lineage determination, embryonic morphogenesis, cancer, and aging. Despite diversity in the nature of the molecular and cellular processes associated with these phenomena, they seem related to the architectural hub of tissue polarity and a need to generate and control this property in a timely manner.