Workflow for ‘Phylogenetic profiling to detect functional linked genes’

 

Summary

The workflow aims to infer functional linkages using phylogenetic profiling. The input protein sequence(s) is usually from any organism with its complete genome sequenced which is searched against proteome data of other organisms with completely sequenced genome using either BLASTP/SSEARCH. The e-values obtained after search of every protein sequence is parsed and normalised and represented as a profile vector/matrix where in the rows are individual proteins and the columns are organisms. The profiles obtained are analysed for their statistical significance using parameters like mutual information content, hamming distance and correlation coefficient.

 

 

Fig: Translated implementation

Standard Tools:

 

·         SSEARCH: Implements MPI version of Smith-Waterman algorithm for database searching and reports the alignment along with statistical significance of the hits obtained.

·         mis_calc: Calculates mutual information content and Pearson Correlation Coefficient of a given profile pair.

·          

Custom Tools:

 

Reads in the results of independent Smith-Waterman database searches and creates a matrix containing normalized E-values.

The SSEARCH output is parsed in terms of % query overlap (default: 40%). The e-value is normalized using the formula normalized e-value=-1/log E 

The tool reads in outputs of independent search (one per organism) and creates a matrix with normalized E-values. The following are some of the assumptions made for the construction of the matrix:

5 --> refers to No significant Hits Found query.

1 --> refers to eVal >= 1

0 --> refers to eVal = 0

2 --> refers to eVal >0 and <1 BUT NOT satisfying conditions.

normaliseEval  --> refers to eVal > 0 and < 1 satisfying conditions.