title: Rapid and enhanced remote homology detection by cascading hidden Markov model searches in sequence space.
abstract: BACKGROUND
  In the post-genomic era, automatic annotation of protein sequences using computational homology-based methods is highly desirable. However, often protein sequences diverge to an extent where detection of homology and automatic annotation transfer is not straightforward. Sophisticated approaches to detect such distant relationships are needed. We propose a new approach to identify deep evolutionary relationships of proteins to overcome shortcomings of the available methods.
  
  
  RESULTS
  We have developed a method to identify remote homologues more effectively from any protein sequence database by using several cascading events with Hidden Markov Models (C-HMM). We have implemented clustering of hits and profile generation of hit clusters to effectively reduce the computational timings of the cascaded sequence searches. Our C-HMM approach could cover 94, 83 and 40% coverage at family, superfamily and fold levels, respectively, when applied on diverse protein folds. We have compared C-HMM with various remote homology detection methods and discuss the trade-offs between coverage and false positives.
  
  
  METHODS
  A standalone package implemented in Java along with a detailed documentation can be downloaded from https://github.com/RSLabNCBS/C-HMM SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
  
  
  BACKGROUND
  mini@ncbs.res.in.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.
authors.forename: Anu G
authors.initials: AG
authors.lastname: Nair
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.
authors.forename: Eshita
authors.initials: E
authors.lastname: Mutt
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.
authors.forename: Hari Prasanna
authors.initials: HP
authors.lastname: Subramanian
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bangalore 560065, India.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Sowdhamini
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D030562:Databases, Protein; D008390:Markov Chains; D011506:Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins