A Fast Alignment-Free Approach for De Novo Detection of Protein Conserved Regions

Armen Abnousi; Shira L Broschat; Ananth Kalyanaraman

doi:10.1371/journal.pone.0161338

A Fast Alignment-Free Approach for De Novo Detection of Protein Conserved Regions

PLoS One. 2016 Aug 23;11(8):e0161338. doi: 10.1371/journal.pone.0161338. eCollection 2016.

Authors

Armen Abnousi¹, Shira L Broschat^{1

2

3}, Ananth Kalyanaraman^{1

2}

Affiliations

¹ School of EECS, Washington State University, Pullman, WA, United States of America.
² Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, United States of America.
³ Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, United States of America.

Abstract

Background: Identifying conserved regions in protein sequences is a fundamental operation, occurring in numerous sequence-driven analysis pipelines. It is used as a way to decode domain-rich regions within proteins, to compute protein clusters, to annotate sequence function, and to compute evolutionary relationships among protein sequences. A number of approaches exist for identifying and characterizing protein families based on their domains, and because domains represent conserved portions of a protein sequence, the primary computation involved in protein family characterization is identification of such conserved regions. However, identifying conserved regions from large collections (millions) of protein sequences presents significant challenges.

Methods: In this paper we present a new, alignment-free method for detecting conserved regions in protein sequences called NADDA (No-Alignment Domain Detection Algorithm). Our method exploits the abundance of exact matching short subsequences (k-mers) to quickly detect conserved regions, and the power of machine learning is used to improve the prediction accuracy of detection. We present a parallel implementation of NADDA using the MapReduce framework and show that our method is highly scalable.

Results: We have compared NADDA with Pfam and InterPro databases. For known domains annotated by Pfam, accuracy is 83%, sensitivity 96%, and specificity 44%. For sequences with new domains not present in the training set an average accuracy of 63% is achieved when compared to Pfam. A boost in results in comparison with InterPro demonstrates the ability of NADDA to capture conserved regions beyond those present in Pfam. We have also compared NADDA with ADDA and MKDOM2, assuming Pfam as ground-truth. On average NADDA shows comparable accuracy, more balanced sensitivity and specificity, and being alignment-free, is significantly faster. Excluding the one-time cost of training, runtimes on a single processor were 49s, 10,566s, and 456s for NADDA, ADDA, and MKDOM2, respectively, for a data set comprised of approximately 2500 sequences.

MeSH terms

Algorithms
Conserved Sequence / genetics*
Databases, Protein
Protein Domains
Protein Structure, Tertiary
Sequence Alignment
Sequence Analysis, Protein*
Sequence Homology, Amino Acid*
Software

Grants and funding

This work was funded by support from the National Science Foundation under the Advances in Biological Informatics program (NSF ABI), Award #1262664 (URL: http://nsf.gov/awardsearch/showAward?AWD_ID=1262664&HistoricalAwards=false). Award is received by SLB and AK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.