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An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a
Raja Jothi1, Teresa M Przytycka, L Aravind
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. jothi@ncbi.nlm.nih.gov
BMC Bioinformatics
|May 25, 2007
Summary
Selecting the right genomes is key for accurate protein functional linkage predictions using phylogenetic profile comparisons (PPCs). Carefully chosen prokaryotic genomes often outperform mixed sets, especially for variable pathways.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- Phylogenetic profile comparisons (PPCs) infer protein function based on co-inheritance.
- This method assumes proteins in the same pathway evolve together.
Purpose of the Study:
- To evaluate the impact of reference genome set composition on PPC accuracy.
- To identify optimal genome sets for predicting functional linkages.
Main Methods:
- Experimentation with E. coli and yeast proteins using 16 diverse reference genome sets.
- Analysis of prediction accuracy across different pathway types and genome compositions.
- Evaluation of a random null model for statistical significance.
Main Results:
- Prokaryotic genomes alone are often sufficient for accurate predictions.
- Adding too many eukaryotes or specific types (parasitic, vertebrate) decreases accuracy.
- Pathway evolutionary history significantly affects optimal reference set choice.
- The standard random null model may yield false positives.
Conclusions:
- Genome set composition, not just size, is critical for PPC accuracy.
- Eukaryotic genomes can be less informative due to endosymbiosis and bacterial contributions.
- Prokaryotic-only sets excel for variable pathways (e.g., metabolism).
- Mixed sets with conserved genomes (e.g., translation) are better for vertically inherited pathways.
- Caution is advised when interpreting large-scale PPC results with a single reference set.
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