2-AIN-505, 2-AIN-251: Seminár z bioinformatiky (1) a (3)
Zima 2016
Abstrakt

Jaina Mistry, Robert D. Finn, Sean R. Eddy, Alex Bateman, Marco Punta. Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions. Nucleic acids research, 41(12):e121. 2013.

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Abstract:

Detection of protein homology via sequence similarity has important applications 
in biology, from protein structure and function prediction to reconstruction of
phylogenies. Although current methods for aligning protein sequences are
powerful, challenges remain, including problems with homologous overextension of 
alignments and with regions under convergent evolution. Here, we test the ability
of the profile hidden Markov model method HMMER3 to correctly assign homologous
sequences to >13,000 manually curated families from the Pfam database. We
identify problem families using protein regions that match two or more Pfam
families not currently annotated as related in Pfam. We find that HMMER3 E-value 
estimates seem to be less accurate for families that feature periodic patterns of
compositional bias, such as the ones typically observed in coiled-coils. These
results support the continued use of manually curated inclusion thresholds in the
Pfam database, especially on the subset of families that have been identified as 
problematic in experiments such as these. They also highlight the need for
developing new methods that can correct for this particular type of compositional
bias.