# FUSE-PhyloTree: linking functions and sequence conservation modules of a protein family through phylogenomic analysis

**Authors:** Olivier Dennler, Elisa Chenel, François Coste, Samuel Blanquart, Catherine Belleannée, Nathalie Théret

PMC · DOI: 10.1093/bioinformatics/btaf479 · 2025-08-28

## TL;DR

FUSE-PhyloTree is a new software that links protein functions with sequence conservation patterns using phylogenetic analysis.

## Contribution

The novelty lies in combining partial local multiple sequence alignment with phylogenetic reconciliation to associate protein functions with sequence modules.

## Key findings

- FUSE-PhyloTree identifies local sequence conservation modules in multi-functional protein families.
- The software annotates gene trees with predicted sequence modules and ancestral gene functions.
- It enables the association of functions with specific sequence regions based on their co-emergence in evolution.

## Abstract

FUSE-PhyloTree is a phylogenomic analysis software for identifying local sequence conservation associated with the different functions of a multi-functional (e.g. paralogous or multi-domain) protein family. FUSE-PhyloTree introduces an original approach that combines advanced sequence analysis with phylogenetic methods. First, local sequence conservation modules within the family are identified using partial local multiple sequence alignment. Next, the evolution of the detected modules and known protein functions is inferred within the family’s phylogenetic tree using three-level phylogenetic reconciliation and ancestral state reconstruction. As a result, FUSE-PhyloTree provides a gene tree annotated with both predicted sequence modules and ancestral gene functions, enabling the association of functions with specific sequence regions based on their co-emergence.

FUSE-PhyloTree is provided as Docker and Singularity images including all the required software tools. Images, source code, test data, and documentation are available at https://github.com/OcMalde/fuse-phylotree and https://zenodo.org/records/15855068.

## Full-text entities

- **Genes:** ADAMTS5 (ADAM metallopeptidase with thrombospondin type 1 motif 5) [NCBI Gene 11096] {aka ADAM-TS 11, ADAM-TS 5, ADAM-TS5, ADAMTS-11, ADAMTS-5, ADAMTS11}, TSL (testis-expressed, seven-twelve, leukemia) [NCBI Gene 790953]
- **Diseases:** MSA (MESH:D010855)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12648394/full.md

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Source: https://tomesphere.com/paper/PMC12648394