From pairs of most similar sequences to phylogenetic best matches

Abstract

Background: Many of the commonly used methods for orthology detection start from mutually most similar pairs of genes (reciprocal best hits) as an approximation for evolutionary most closely related pairs of genes (reciprocal best matches). This approximation of best matches by best hits becomes exact for ultrametric dissimilarities, i.e., under the Molecular Clock Hypothesis. It fails, however, whenever there are large lineage specific rate variations among paralogous genes. In practice, this introduces a high level of noise into the input data for best-hit-based orthology detection methods.Results: If additive distances between genes are known, then evolutionary most closely related pairs can be identified by considering certain quartets of genes provided that in each quartet the outgroup relative to the remaining three genes is known. A priori knowledge of underlying species phylogeny greatly facilitates the identification of the required outgroup. Although the workflow remains a heuristic since the correct outgroup cannot be determined reliably in all cases, simulations with lineage specific biases and rate asymmetries show that nearly perfect results can be achieved. In a realistic setting, where distances data have to be estimated from sequence data and hence are noisy, it is still possible to obtain highly accurate sets of best matches.Conclusion: Improvements of tree-free orthology assessment methods can be expected from a combination of the accurate inference of best matches reported here and recent mathematical advances in the understanding of (reciprocal) best match graphs and orthology relations.Availability: Accompanying software is available at https ://githu b.com/david -schal ler/Asymm eTree .

Complete Characterization of Incorrect Orthology Assignments in Best Match Graphs

“…There are, however, two distinct sources of errors in an orthology assignment pipeline based on best matches: inaccuracies in the assignment of best matches from sequence similarity data Stadler et al. ( 2020 ), and limits in the reconstruction of the “true” orthology relation from best match graphs Geiß et al. ( 2020b ).…”

“…inaccuracies in the assignment of best matches from sequence similarity data Stadler et al. ( 2020 ), and…”

“…In practice, best matches are approximated by sequence similarity and thus are subject to noise and biases Stadler et al. ( 2020 ). The empirically determined best match relation thus will usually need to be corrected to conform to the formal definition (cf.…”

Reconstruction of time-consistent species trees

“…To some extent, these relations can be estimated directly from sequence data using a variety of algorithmic approaches that are based on the pairwise best match Lafond and Hellmuth Algorithms Mol Biol (2020) 15:16 criterion [8][9][10][11] and hence do not require any a priori knowledge of the topology of either the gene tree or the species tree. Practical workflows for orthology assignment directly use pairwise best matches as an initial estimate of orthologous gene pairs.…”

Reconstruction of time-consistent species trees

“…To some extent, these relations can be estimated directly from sequence data using a variety of algorithmic approaches that are based on the pairwise best match criterion [8][9][10][11] and hence do not require any a priori knowledge of the topology of either the gene tree or the species tree. Practical workflows for orthology assignment directly use pairwise best matches as an initial estimate of orthologous gene pairs.…”