Cladograms with Path to Event (ClaPTE): a novel algorithm to detect associations between genotypes or phenotypes...

Area of Science:

• Evolutionary biology
• Genetics
• Bioinformatics

Background:

• Genotype-phenotype associations reveal pathogen evolution, drug resistance, and transmission dynamics.
• Common ancestry can create spurious associations between unrelated traits.
• Phylogenetic tree analysis is crucial for understanding these evolutionary relationships.

Purpose of the Study:

• To introduce Cladograms with Path to Event (ClaPTE), a novel method for detecting character-pair associations.
• To adjust for common ancestry when identifying genotype-phenotype relationships.
• To compare ClaPTE's performance against existing phylogenetic association methods.

Main Methods:

• ClaPTE identifies character-pairs exhibiting co-evolutionary patterns on phylogenetic trees.
• The method was evaluated using simulations on gene trees (HIV Env, HIV promoter, bacterial DnaJ, GuaB) and case studies (Influenza/Oseltamavir resistance, DnaJ, GuaB).
• Performance was assessed by comparing ClaPTE to independent contrasts, mixed models, and likelihood ratio tests, focusing on type I and type II error rates.

Main Results:

• ClaPTE demonstrates competitive sensitivity and superior type I error control compared to existing methods.
• In the Influenza case study, ClaPTE identified associations between adjacent amino acid positions missed by other methods.
• For DnaJ and GuaB, ClaPTE found more associations within protein families than between them, aligning with biological expectations.

Conclusions:

• ClaPTE is a robust method for detecting biologically plausible genotype-phenotype associations.
• The method effectively corrects for common ancestry, providing more reliable insights into pathogen evolution.
• ClaPTE offers an advancement in analyzing complex evolutionary relationships in molecular data.