A reproducibility analysis-based statistical framework for residue-residue evolutionary coupling detection
Yunda Si1, Yi Zhang1, Chengfei Yan1
1School of Physics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Briefings in Bioinformatics
|January 17, 2022
Summary
We developed irreproducible discovery rate (IDR)-DCA, a new framework to reliably detect significant evolutionary couplings from direct coupling analysis (DCA). This method improves residue pair selection for predicting protein and RNA structures.
Area of Science:
- Bioinformatics
- Computational Biology
- Structural Biology
Background:
- Direct Coupling Analysis (DCA) infers evolutionary coupled residue pairs from Multiple Sequence Alignments (MSAs).
- Selecting significant residue pairs from DCA results is challenging.
- Existing methods often require careful tuning of coupling score cutoffs.
Purpose of the Study:
- To develop a robust statistical framework for detecting significant evolutionary couplings.
- To improve the selection of residue pairs for contact prediction in proteins and RNAs.
- To enhance the reliability and performance of DCA-based predictions.
Main Methods:
- Developed irreproducible discovery rate (IDR)-DCA, a framework based on reproducibility analysis of DCA coupling scores.
- Applied IDR-DCA to manually created MSA replicates.
- Tested IDR-DCA with three DCA versions for contact prediction in monomeric proteins, protein-protein interactions, and monomeric RNAs.
- Performed MSA downsampling analysis to assess robustness.
Main Results:
- IDR-DCA enabled stable contact prediction performance using a universal threshold across different DCA methods.
- IDR-DCA consistently outperformed carefully tuned coupling score cutoffs.
- The framework demonstrated robustness through MSA downsampling.
- Constraints from IDR-DCA selected pairs effectively assisted RNA secondary structure prediction.
Conclusions:
- IDR-DCA provides a general and reliable statistical framework for evolutionary coupling detection.
- This method enhances the accuracy and stability of contact prediction for various biological molecules.
- IDR-DCA offers a significant improvement over traditional DCA result interpretation.
More Related Videos
Related Concept Videos
02:54Evolutionary Relationships through Genome Comparisons
6.4K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
6.4K
02:53Conservative Site-specific Recombination and Phase Variation
6.2K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.2K
02:02Cis-regulatory Sequences
10.8K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
10.8K
01:29Protein Folding Quality Check in the RER
4.0K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.0K