Prediction of multi-drug resistance transporters using a novel sequence analysis method
Abstract
There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequence similarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.
- Authors:
-
[1];
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Oregon Health & Science Univ., Portland, OR (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1214792
- Alternate Identifier(s):
- OSTI ID: 1813736
- Report Number(s):
- PNNL-SA-108738
Journal ID: ISSN 2046-1402
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- F1000Research
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: C; Journal ID: ISSN 2046-1402
- Publisher:
- F1000Research
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; machine learning; antibiotic resistance; microbiome; bacteria; protein function
Citation Formats
McDermott, Jason E., Bruillard, Paul J., Overall, Christopher C., Gosink, Luke J., and Lindemann, Stephen R. Prediction of multi-drug resistance transporters using a novel sequence analysis method. United States: N. p., 2015.
Web. doi:10.12688/f1000research.6200.2.
McDermott, Jason E., Bruillard, Paul J., Overall, Christopher C., Gosink, Luke J., & Lindemann, Stephen R. Prediction of multi-drug resistance transporters using a novel sequence analysis method. United States. https://doi.org/10.12688/f1000research.6200.2
McDermott, Jason E., Bruillard, Paul J., Overall, Christopher C., Gosink, Luke J., and Lindemann, Stephen R. Mon .
"Prediction of multi-drug resistance transporters using a novel sequence analysis method". United States. https://doi.org/10.12688/f1000research.6200.2. https://www.osti.gov/servlets/purl/1214792.
@article{osti_1214792,
title = {Prediction of multi-drug resistance transporters using a novel sequence analysis method},
author = {McDermott, Jason E. and Bruillard, Paul J. and Overall, Christopher C. and Gosink, Luke J. and Lindemann, Stephen R.},
abstractNote = {There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequence similarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.},
doi = {10.12688/f1000research.6200.2},
journal = {F1000Research},
number = C,
volume = 6,
place = {United States},
year = {Mon Mar 09 00:00:00 EDT 2015},
month = {Mon Mar 09 00:00:00 EDT 2015}
}
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Works referenced in this record:
Expanding the soil antibiotic resistome: exploring environmental diversity
journal, October 2007
- D’Costa, Vanessa M.; Griffiths, Emma; Wright, Gerard D.
- Current Opinion in Microbiology, Vol. 10, Issue 5, p. 481-489
The Pfam Protein Families Database
journal, January 2000
- Bateman, A.
- Nucleic Acids Research, Vol. 28, Issue 1
IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth
journal, April 2012
- Peng, Y.; Leung, H. C. M.; Yiu, S. M.
- Bioinformatics, Vol. 28, Issue 11
Multidrug-resistance efflux pumps ? not just for resistance
journal, August 2006
- Piddock, Laura J. V.
- Nature Reviews Microbiology, Vol. 4, Issue 8
Accurate Prediction of Secreted Substrates and Identification of a Conserved Putative Secretion Signal for Type III Secretion Systems
journal, April 2009
- Samudrala, Ram; Heffron, Fred; McDermott, Jason E.
- PLoS Pathogens, Vol. 5, Issue 4
Automatic Feature Generation for Machine Learning Based Optimizing Compilation
conference, March 2009
- Leather, Hugh; Bonilla, Edwin; O'Boyle, Michael
- 2009 7th Annual IEEE/ACM International Symposium on Code Generation and Optimization (CGO), 2009 International Symposium on Code Generation and Optimization
The epsomitic phototrophic microbial mat of Hot Lake, Washington: community structural responses to seasonal cycling
journal, January 2013
- Lindemann, Stephen R.; Moran, James J.; Stegen, James C.
- Frontiers in Microbiology, Vol. 4
Classifying Substrate Specificities of Membrane Transporters from Arabidopsis thaliana
journal, September 2010
- Schaadt, Nadine S.; Christoph, Jan; Helms, Volkhard
- Journal of Chemical Information and Modeling, Vol. 50, Issue 10
Molecular mechanisms of antibiotic resistance
journal, December 2014
- Blair, Jessica M. A.; Webber, Mark A.; Baylay, Alison J.
- Nature Reviews Microbiology, Vol. 13, Issue 1
Evolving stochastic context--free grammars for RNA secondary structure prediction
journal, January 2012
- WJ Anderson, James; Tataru, Paula; Staines, Joe
- BMC Bioinformatics, Vol. 13, Issue 1
The PROSITE database, its status in 1999
journal, January 1999
- Hofmann, K.; Bucher, P.; Falquet, L.
- Nucleic Acids Research, Vol. 27, Issue 1
Transferring functional annotations of membrane transporters on the basis of sequence similarity and sequence motifs
journal, November 2013
- Barghash, Ahmad; Helms, Volkhard
- BMC Bioinformatics, Vol. 14, Issue 1
Prediction of protein folding class using global description of amino acid sequence.
journal, September 1995
- Dubchak, I.; Muchnik, I.; Holbrook, S. R.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 19
The Transporter Classification Database
journal, November 2013
- Saier, Milton H.; Reddy, Vamsee S.; Tamang, Dorjee G.
- Nucleic Acids Research, Vol. 42, Issue D1
Fast gapped-read alignment with Bowtie 2
journal, March 2012
- Langmead, Ben; Salzberg, Steven L.
- Nature Methods, Vol. 9, Issue 4
Trimmomatic: a flexible trimmer for Illumina sequence data
journal, April 2014
- Bolger, Anthony M.; Lohse, Marc; Usadel, Bjoern
- Bioinformatics, Vol. 30, Issue 15
Functional classification of membrane transporters and channels based on filtered TM/non-TM amino acid composition
journal, April 2012
- Schaadt, N. S.; Helms, V.
- Biopolymers, Vol. 97, Issue 7
The Shared Antibiotic Resistome of Soil Bacteria and Human Pathogens
journal, August 2012
- Forsberg, K. J.; Reyes, A.; Wang, B.
- Science, Vol. 337, Issue 6098
Structure of the Multidrug Transporter EmrD from Escherichia coli
journal, May 2006
- Yin, Y.
- Science, Vol. 312, Issue 5774
Multidrug Resistance in Bacteria
journal, June 2009
- Nikaido, Hiroshi
- Annual Review of Biochemistry, Vol. 78, Issue 1
Evolution and ecology of antibiotic resistance genes
journal, June 2007
- Aminov, Rustam I.; Mackie, Roderick I.
- FEMS Microbiology Letters, Vol. 271, Issue 2
Prodigal: prokaryotic gene recognition and translation initiation site identification
journal, March 2010
- Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F.
- BMC Bioinformatics, Vol. 11, Issue 1
Computational Prediction of Type III and IV Secreted Effectors in Gram-Negative Bacteria
journal, October 2010
- McDermott, Jason E.; Corrigan, Abigail; Peterson, Elena
- Infection and Immunity, Vol. 79, Issue 1
Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria
journal, March 2012
- Nikaido, Hiroshi; Pagès, Jean-Marie
- FEMS Microbiology Reviews, Vol. 36, Issue 2
SUPERFAMILY: HMMs representing all proteins of known structure. SCOP sequence searches, alignments and genome assignments
journal, January 2002
- Gough, J.
- Nucleic Acids Research, Vol. 30, Issue 1
The Sequence Alignment/Map format and SAMtools
journal, June 2009
- Li, H.; Handsaker, B.; Wysoker, A.
- Bioinformatics, Vol. 25, Issue 16
IMG ER: a system for microbial genome annotation expert review and curation
journal, June 2009
- Markowitz, Victor M.; Mavromatis, Konstantinos; Ivanova, Natalia N.
- Bioinformatics, Vol. 25, Issue 17
Prediction of multi-drug resistance transporters dataset
dataset, January 2015
- McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.
- f1000research.com
Phototrophic biofilm assembly in microbial-mat-derived unicyanobacterial consortia: model systems for the study of autotroph-heterotroph interactions
journal, April 2014
- Cole, Jessica K.; Hutchison, Janine R.; Renslow, Ryan S.
- Frontiers in Microbiology, Vol. 5
Probabilistic grammatical model for helix‐helix contact site classification
journal, December 2013
- Dyrka, Witold; Nebel, Jean‐Christophe; Kotulska, Malgorzata
- Algorithms for Molecular Biology, Vol. 8, Issue 1
propy: a tool to generate various modes of Chou’s PseAAC
journal, February 2013
- Cao, Dong-Sheng; Xu, Qing-Song; Liang, Yi-Zeng
- Bioinformatics, Vol. 29, Issue 7
Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems
journal, March 2009
- Martinez, Jose Luis; Sánchez, María Blanca; Martínez-Solano, Laura
- FEMS Microbiology Reviews, Vol. 33, Issue 2
Functional classification of membrane transporters and channels based on filtered TM/non-TM amino acid composition
journal, April 2012
- Schaadt, N. S.; Helms, V.
- Biopolymers, Vol. 97, Issue 7
Classifying Substrate Specificities of Membrane Transporters from Arabidopsis Thaliana
journal, February 2011
- Schaadt, Nadine S.; Christoph, Jan; Helms, Volkhard
- Biophysical Journal, Vol. 100, Issue 3
Expanding the soil antibiotic resistome: exploring environmental diversity
journal, October 2007
- D’Costa, Vanessa M.; Griffiths, Emma; Wright, Gerard D.
- Current Opinion in Microbiology, Vol. 10, Issue 5, p. 481-489
Multidrug-resistance efflux pumps ? not just for resistance
journal, August 2006
- Piddock, Laura J. V.
- Nature Reviews Microbiology, Vol. 4, Issue 8
Molecular mechanisms of antibiotic resistance
journal, December 2014
- Blair, Jessica M. A.; Webber, Mark A.; Baylay, Alison J.
- Nature Reviews Microbiology, Vol. 13, Issue 1
Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens
journal, March 2021
- Papalexi, Efthymia; Mimitou, Eleni P.; Butler, Andrew W.
- Nature Genetics, Vol. 53, Issue 3
CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis
journal, September 2019
- Mandal, Malay; Okoreeh, Michael K.; Kennedy, Domenick E.
- Nature Immunology, Vol. 20, Issue 10
Prediction of protein folding class using global description of amino acid sequence.
journal, September 1995
- Dubchak, I.; Muchnik, I.; Holbrook, S. R.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 19
The DrrAB Efflux System of Streptomyces peucetius Is a Multidrug Transporter of Broad Substrate Specificity
journal, March 2014
- Li, Wen; Sharma, Madhu; Kaur, Parjit
- Journal of Biological Chemistry, Vol. 289, Issue 18
IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth
journal, April 2012
- Peng, Y.; Leung, H. C. M.; Yiu, S. M.
- Bioinformatics, Vol. 28, Issue 11
propy: a tool to generate various modes of Chou’s PseAAC
journal, February 2013
- Cao, Dong-Sheng; Xu, Qing-Song; Liang, Yi-Zeng
- Bioinformatics, Vol. 29, Issue 7
The Pfam Protein Families Database
journal, January 2000
- Bateman, A.
- Nucleic Acids Research, Vol. 28, Issue 1
Evolution and ecology of antibiotic resistance genes
journal, June 2007
- Aminov, Rustam I.; Mackie, Roderick I.
- FEMS Microbiology Letters, Vol. 271, Issue 2
Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems
journal, March 2009
- Martinez, Jose Luis; Sánchez, María Blanca; Martínez-Solano, Laura
- FEMS Microbiology Reviews, Vol. 33, Issue 2
Structure of the Multidrug Transporter EmrD from Escherichia coli
journal, May 2006
- Yin, Y.
- Science, Vol. 312, Issue 5774
Prodigal: prokaryotic gene recognition and translation initiation site identification
journal, March 2010
- Hyatt, Doug; Chen, Gwo-Liang; LoCascio, Philip F.
- BMC Bioinformatics, Vol. 11, Issue 1
Evolving stochastic context--free grammars for RNA secondary structure prediction
journal, January 2012
- WJ Anderson, James; Tataru, Paula; Staines, Joe
- BMC Bioinformatics, Vol. 13, Issue 1
Transferring functional annotations of membrane transporters on the basis of sequence similarity and sequence motifs
journal, November 2013
- Barghash, Ahmad; Helms, Volkhard
- BMC Bioinformatics, Vol. 14, Issue 1
Probabilistic grammatical model for helix‐helix contact site classification
journal, December 2013
- Dyrka, Witold; Nebel, Jean‐Christophe; Kotulska, Malgorzata
- Algorithms for Molecular Biology, Vol. 8, Issue 1
The epsomitic phototrophic microbial mat of Hot Lake, Washington: community structural responses to seasonal cycling
journal, January 2013
- Lindemann, Stephen R.; Moran, James J.; Stegen, James C.
- Frontiers in Microbiology, Vol. 4
Phototrophic biofilm assembly in microbial-mat-derived unicyanobacterial consortia: model systems for the study of autotroph-heterotroph interactions
journal, April 2014
- Cole, Jessica K.; Hutchison, Janine R.; Renslow, Ryan S.
- Frontiers in Microbiology, Vol. 5
Prediction of multi-drug resistance transporters dataset
dataset, January 2015
- McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.
- f1000research.com
Prediction of multi-drug resistance transporters dataset
dataset, January 2015
- McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.
- f1000research.com
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