Size distribution of function-based human gene sets and the split–merge model

• Main Authors: Wentian Li, Oscar Fontanelli, Pedro Miramontes
• Format: Article
• Language: English
• Published: The Royal Society 2016-01-01
• Series: Royal Society Open Science
• Subjects: gene family sizes; gene set sizes; power-law; beta rank function
• Online Access: https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.160275

The sizes of paralogues—gene families produced by ancestral duplication—are known to follow a power-law distribution. We examine the size distribution of gene sets or gene families where genes are grouped by a similar function or share a common property. The size distribution of Human Gene Nomenclature Committee (HGNC) gene sets deviate from the power-law, and can be fitted much better by a beta rank function. We propose a simple mechanism to break a power-law size distribution by a combination of splitting and merging operations. The largest gene sets are split into two to account for the subfunctional categories, and a small proportion of other gene sets are merged into larger sets as new common themes might be realized. These operations are not uncommon for a curator of gene sets. A simulation shows that iteration of these operations changes the size distribution of Ensembl paralogues and could lead to a distribution fitted by a rank beta function. We further illustrate application of beta rank function by the example of distribution of transcription factors and drug target genes among HGNC gene families.