Simple and thorough detection of related sequences with position-varying probabilities of substitutions, insertions, and deletions

Abstract

One way to understand biology is by finding genetic sequences that are related to each other. Often, a family of related sequences has position-varying probabilities of substitutions, insertions, and deletions: we can use these to find distantly-related sequences. There are popular software tools for this task, which all have limitations. They either do not use all probability evidence (e.g. PSI-BLAST, MMseqs2), or have excessive complexity and minor biases (e.g. HMMER). This complexity inhibits fertile development of alternative tools. This study describes a simplest reasonable way to find related sequences, making full use of position-varying probabilities. The algorithms likely use the fewest operations that such algorithms possibly could, so they are fast and simple. This has been implemented in prototype software named DUMMER (Dumb Uncomplicated Match ModelER). Its sensitivity and specificity are competitive with HMMER. It finds evidence that the human genome has vastly more relics of LF-SINE, retrotransposons that were co-opted for various functions in common ancestors of all land vertebrates.