Deeplasmid: deep learning accurately separates plasmids from bacterial chromosomes

Andreopoulos, William B.; Geller, Alexander M.; Lucke, Miriam; Balewski, Jan; Clum, Alicia; Ivanova, Natalia N.; Levy, Asaf

doi:10.1093/nar/gkab1115

Deeplasmid: deep learning accurately separates plasmids from bacterial chromosomes

Journal Article · Mon Dec 06 00:00:00 EST 2021 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkab1115· OSTI ID:1894067

Andreopoulos, William B. ^[1]; Geller, Alexander M. ^[2]; Lucke, Miriam ^[2]; Balewski, Jan ^[3]; Clum, Alicia ^[4]; Ivanova, Natalia N. ^[4]; ^[2]

USDOE Joint Genome Institute (JGI), Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); San Jose State Univ., CA (United States)
Hebrew Univ. of Jerusalem (Israel)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
USDOE Joint Genome Institute (JGI), Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Plasmids are mobile genetic elements that play a key role in microbial ecology and evolution by mediating horizontal transfer of important genes, such as antimicrobial resistance genes. Many microbial genomes have been sequenced by short read sequencers and have resulted in a mix of contigs that derive from plasmids or chromosomes. New tools that accurately identify plasmids are needed to elucidate new plasmid-borne genes of high biological importance. We have developed Deeplasmid, a deep learning tool for distinguishing plasmids from bacterial chromosomes based on the DNA sequence and its encoded biological data. It requires as input only assembled sequences generated by any sequencing platform and assembly algorithm and its runtime scales linearly with the number of assembled sequences. Deeplasmid achieves an AUC–ROC of over 89%, and it was more accurate than five other plasmid classification methods. Finally, as a proof of concept, we used Deeplasmid to predict new plasmids in the fish pathogen Yersinia ruckeri ATCC 29473 that has no annotated plasmids. Deeplasmid predicted with high reliability that a long assembled contig is part of a plasmid. Using long read sequencing we indeed validated the existence of a 102 kb long plasmid, demonstrating Deeplasmid's ability to detect novel plasmids.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: Israeli Ministry of Agriculture; Israeli Science Foundation; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1894067

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 3 Vol. 50; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (55)

Post-transcriptional control of expression of the repA gene of plasmid R1 mediated by a small RNA molecule. Light, J.; Molin, S. The EMBO Journal, Vol. 2, Issue 1 https://doi.org/10.1002/j.1460-2075.1983.tb01387.x	journal	January 1983
Quinolone resistance from a transferable plasmid Martínez-Martínez, Luis; Pascual, Alvaro; Jacoby, George A. The Lancet, Vol. 351, Issue 9105 https://doi.org/10.1016/S0140-6736(97)07322-4	journal	March 1998
Base composition bias might result from competition for metabolic resources Rocha, Eduardo P. C.; Danchin, Antoine Trends in Genetics, Vol. 18, Issue 6 https://doi.org/10.1016/S0168-9525(02)02690-2	journal	June 2002
An SOS Inhibitor that Binds to Free RecA Protein: The PsiB Protein Petrova, Vessela; Chitteni-Pattu, Sindhu; Drees, Julia C. Molecular Cell, Vol. 36, Issue 1 https://doi.org/10.1016/j.molcel.2009.07.026	journal	October 2009
Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko Molecular Cell, Vol. 70, Issue 5 https://doi.org/10.1016/j.molcel.2018.01.003	journal	June 2018
Ordering the mob: Insights into replicon and MOB typing schemes from analysis of a curated dataset of publicly available plasmids Orlek, Alex; Phan, Hang; Sheppard, Anna E. Plasmid, Vol. 91 https://doi.org/10.1016/j.plasmid.2017.03.002	journal	May 2017
Introducing the bacterial ‘chromid’: not a chromosome, not a plasmid Harrison, Peter W.; Lower, Ryan P. J.; Kim, Nayoung K. D. Trends in Microbiology, Vol. 18, Issue 4 https://doi.org/10.1016/j.tim.2009.12.010	journal	April 2010
Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes Shafin, Kishwar; Pesout, Trevor; Lorig-Roach, Ryan Nature Biotechnology, Vol. 38, Issue 9 https://doi.org/10.1038/s41587-020-0503-6	journal	May 2020
Plasmid and chromosome partitioning: surprises from phylogeny: Phylogeny of partitioning ATPases Gerdes, Kenn; Møller-Jensen, Jakob; Jensen, Rasmus Bugge Molecular Microbiology, Vol. 37, Issue 3 https://doi.org/10.1046/j.1365-2958.2000.01975.x	journal	August 2000
Mechanism of plasmid-mediated quinolone resistance Tran, John H.; Jacoby, George A. Proceedings of the National Academy of Sciences, Vol. 99, Issue 8 https://doi.org/10.1073/pnas.082092899	journal	April 2002
DNA Features Viewer: a sequence annotation formatting and plotting library for Python Zulkower, Valentin; Rosser, Susan Bioinformatics, Vol. 36, Issue 15 https://doi.org/10.1093/bioinformatics/btaa213	journal	July 2020
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences Li, W.; Godzik, A. Bioinformatics, Vol. 22, Issue 13 https://doi.org/10.1093/bioinformatics/btl158	journal	May 2006
cBar: a computer program to distinguish plasmid-derived from chromosome-derived sequence fragments in metagenomics data Zhou, Fengfeng; Xu, Ying Bioinformatics, Vol. 26, Issue 16 https://doi.org/10.1093/bioinformatics/btq299	journal	August 2010
plasmidSPAdes: assembling plasmids from whole genome sequencing data Antipov, Dmitry; Hartwick, Nolan; Shen, Max Bioinformatics https://doi.org/10.1093/bioinformatics/btw493	journal	July 2016
Recycler: an algorithm for detecting plasmids from de novo assembly graphs Rozov, Roye; Brown Kav, Aya; Bogumil, David Bioinformatics https://doi.org/10.1093/bioinformatics/btw651	journal	December 2016
PLACNETw: a web-based tool for plasmid reconstruction from bacterial genomes Vielva, Luis; de Toro, María; Lanza, Val F. Bioinformatics, Vol. 33, Issue 23 https://doi.org/10.1093/bioinformatics/btx462	journal	July 2017
Minimap2: pairwise alignment for nucleotide sequences Li, Heng Bioinformatics, Vol. 34, Issue 18 https://doi.org/10.1093/bioinformatics/bty191	journal	May 2018
HyAsP, a greedy tool for plasmids identification Müller, Robert; Chauve, Cedric Bioinformatics, Vol. 35, Issue 21 https://doi.org/10.1093/bioinformatics/btz413	journal	May 2019
The IMG/M data management and analysis system v.6.0: new tools and advanced capabilities Chen, I-Min A.; Chu, Ken; Palaniappan, Krishnaveni Nucleic Acids Research, Vol. 49, Issue D1 https://doi.org/10.1093/nar/gkaa939	journal	October 2020
NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins Pruitt, K. D.; Tatusova, T.; Maglott, D. R. Nucleic Acids Research, Vol. 35, Issue Database https://doi.org/10.1093/nar/gkl842	journal	January 2007
ACLAME: A CLAssification of Mobile genetic Elements, update 2010 Leplae, Raphaël; Lima-Mendez, Gipsi; Toussaint, Ariane Nucleic Acids Research, Vol. 38, Issue suppl_1 https://doi.org/10.1093/nar/gkp938	journal	November 2009
IMG: the integrated microbial genomes database and comparative analysis system Markowitz, V. M.; Chen, I. -M. A.; Palaniappan, K. Nucleic Acids Research, Vol. 40, Issue D1 https://doi.org/10.1093/nar/gkr1044	journal	December 2011
PlasFlow: predicting plasmid sequences in metagenomic data using genome signatures Krawczyk, Pawel S.; Lipinski, Leszek; Dziembowski, Andrzej Nucleic Acids Research, Vol. 46, Issue 6 https://doi.org/10.1093/nar/gkx1321	journal	January 2018
PLSDB: a resource of complete bacterial plasmids Galata, Valentina; Fehlmann, Tobias; Backes, Christina Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky1050	journal	October 2018
IMG/M v.5.0: an integrated data management and comparative analysis system for microbial genomes and microbiomes Chen, I-Min A.; Chu, Ken; Palaniappan, Krishna Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky901	journal	October 2018
Plasmid-Mediated Adhesion in Enteropathogenic Escherichia coli Baldini, Mary M.; Kaper, James B.; Levine, Myron M. Journal of Pediatric Gastroenterology and Nutrition, Vol. 2, Issue 3 https://doi.org/10.1097/00005176-198302030-00023	journal	August 1983
A vast collection of microbial genes that are toxic to bacteria Kimelman, A.; Levy, A.; Sberro, H. Genome Research, Vol. 22, Issue 4 https://doi.org/10.1101/gr.133850.111	journal	February 2012
Canu: scalable and accurate long-read assembly via adaptive k -mer weighting and repeat separation Koren, Sergey; Walenz, Brian P.; Berlin, Konstantin Genome Research, Vol. 27, Issue 5 https://doi.org/10.1101/gr.215087.116	journal	March 2017
Plasmid detection and assembly in genomic and metagenomic data sets Antipov, Dmitry; Raiko, Mikhail; Lapidus, Alla Genome Research, Vol. 29, Issue 6 https://doi.org/10.1101/gr.241299.118	journal	May 2019
Microreview: Type IV secretion systems: versatility and diversity in function: Diversity and versatility of the type IV secretion system Wallden, Karin; Rivera-Calzada, Angel; Waksman, Gabriel Cellular Microbiology, Vol. 12, Issue 9 https://doi.org/10.1111/j.1462-5822.2010.01499.x	journal	July 2010
Plasmid-directed mechanisms for bacteriophage defense in lactic streptococci Klaenhammer, Todd R. FEMS Microbiology Letters, Vol. 46, Issue 3 https://doi.org/10.1111/j.1574-6968.1987.tb02468.x	journal	September 1987
Control of genes for conjugative transfer of plasmids and other mobile elements Zatyka, Malgorzata; Thomas, Christopher M. FEMS Microbiology Reviews, Vol. 21, Issue 4 https://doi.org/10.1111/j.1574-6976.1998.tb00355.x	journal	February 1998
The diversity of conjugative relaxases and its application in plasmid classification Garcillán-Barcia, María Pilar; Francia, María Victoria; de La Cruz, Fernando FEMS Microbiology Reviews, Vol. 33, Issue 3 https://doi.org/10.1111/j.1574-6976.2009.00168.x	journal	May 2009
Genome-Wide Experimental Determination of Barriers to Horizontal Gene Transfer Sorek, R.; Zhu, Y.; Creevey, C. J. Science, Vol. 318, Issue 5855 https://doi.org/10.1126/science.1147112	journal	November 2007
In Silico Detection and Typing of Plasmids using PlasmidFinder and Plasmid Multilocus Sequence Typing Carattoli, Alessandra; Zankari, Ea; García-Fernández, Aurora Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 7 https://doi.org/10.1128/AAC.02412-14	journal	April 2014
The Pseudomonas aeruginosa Pathogenicity Island PAPI-1 Is Transferred via a Novel Type IV Pilus Carter, Michelle Qiu; Chen, Jianshun; Lory, Stephen Journal of Bacteriology, Vol. 192, Issue 13 https://doi.org/10.1128/JB.00041-10	journal	July 2010
Mobility of Plasmids Smillie, C.; Garcillan-Barcia, M. P.; Francia, M. V. Microbiology and Molecular Biology Reviews, Vol. 74, Issue 3 https://doi.org/10.1128/MMBR.00020-10	journal	August 2010
Toxin Plasmids of Clostridium perfringens Li, Jihong; Adams, Vicki; Bannam, Trudi L. Microbiology and Molecular Biology Reviews, Vol. 77, Issue 2 https://doi.org/10.1128/MMBR.00062-12	journal	June 2013
Genome Sequence of Burkholderia pseudomallei NCTC 13392 Sahl, Jason W.; Stone, Joshua K.; Gelhaus, H. Carl Genome Announcements, Vol. 1, Issue 3 https://doi.org/10.1128/genomeA.00183-13	journal	June 2013
Sequence Determination of Burkholderia pseudomallei Strain NCTC 13392 Colony Morphology Variants Vipond, Julia; Kane, Jennifer; Hatch, Graham Genome Announcements, Vol. 1, Issue 6 https://doi.org/10.1128/genomeA.00925-13	journal	December 2013
Whole-Genome Yersinia sp. Assemblies from 10 Diverse Strains Daligault, H. E.; Davenport, K. W.; Minogue, T. D. Genome Announcements, Vol. 2, Issue 5 https://doi.org/10.1128/genomeA.01055-14	journal	October 2014
Plasmid required for virulence of Agrobacterium tumefaciens Watson, B.; Currier, T. C.; Gordon, M. P. Journal of Bacteriology, Vol. 123, Issue 1 https://doi.org/10.1128/jb.123.1.255-264.1975	journal	July 1975
Mode of infection, nodulation specificity, and indigenous plasmids of 11 fast-growing Rhizobium japonicum strains Heron, D. S.; Pueppke, S. G. Journal of Bacteriology, Vol. 160, Issue 3 https://doi.org/10.1128/jb.160.3.1061-1066.1984	journal	December 1984
Characterization of a plasmid-specified pathway for catabolism of isopropylbenzene in Pseudomonas putida RE204 Eaton, R. W.; Timmis, K. N. Journal of Bacteriology, Vol. 168, Issue 1 https://doi.org/10.1128/jb.168.1.123-131.1986	journal	October 1986
Broad-host-range properties of plasmid RK2: importance of overlapping genes encoding the plasmid replication initiation protein TrfA Fang, F. C.; Helinski, D. R. Journal of Bacteriology, Vol. 173, Issue 18 https://doi.org/10.1128/jb.173.18.5861-5868.1991	journal	September 1991
Interactions of the origin of replication (oriV) and initiation proteins (TrfA) of plasmid RK2 with submembrane domains of Escherichia coli Mei, J.; Benashski, S.; Firshein, W. Journal of Bacteriology, Vol. 177, Issue 23 https://doi.org/10.1128/jb.177.23.6766-6772.1995	journal	December 1995
A computational model for TensorFlow: an introduction Abadi, Martín; Isard, Michael; Murray, Derek G. Proceedings of the 1st ACM SIGPLAN International Workshop on Machine Learning and Programming Languages https://doi.org/10.1145/3088525.3088527	conference	June 2017
Plasmid-Mediated Heavy Metal Resistances Silver, S.; Misra, T. K. Annual Review of Microbiology, Vol. 42, Issue 1 https://doi.org/10.1146/annurev.mi.42.100188.003441	journal	October 1988
Learning to Forget: Continual Prediction with LSTM Gers, Felix A.; Schmidhuber, Jürgen; Cummins, Fred Neural Computation, Vol. 12, Issue 10 https://doi.org/10.1162/089976600300015015	journal	October 2000
Mob/oriT, a mobilizable site-specific recombination system for unmarked genetic manipulation in Bacillus thuringiensis and Bacillus cereus Wang, Pengxia; Zhu, Yiguang; Zhang, Yuyang Microbial Cell Factories, Vol. 15, Issue 1 https://doi.org/10.1186/s12934-016-0492-9	journal	June 2016
The stb Operon Balances the Requirements for Vegetative Stability and Conjugative Transfer of Plasmid R388 Guynet, Catherine; Cuevas, Ana; Moncalián, Gabriel PLoS Genetics, Vol. 7, Issue 5 https://doi.org/10.1371/journal.pgen.1002073	journal	May 2011
pYR4 From a Norwegian Isolate of Yersinia ruckeri Is a Putative Virulence Plasmid Encoding Both a Type IV Pilus and a Type IV Secretion System Wrobel, Agnieszka; Ottoni, Claudio; Leo, Jack C. Frontiers in Cellular and Infection Microbiology, Vol. 8 https://doi.org/10.3389/fcimb.2018.00373	journal	October 2018
Toxin–antitoxin systems: Biology, identification, and application Unterholzner, Simon J.; Poppenberger, Brigitte; Rozhon, Wilfried Mobile Genetic Elements, Vol. 3, Issue 5 https://doi.org/10.4161/mge.26219	journal	September 2013
Mob/oriT, a mobilizable site-specific recombination system for unmarked genetic manipulation in Bacillus thuringiensis and Bacillus cereus Wang, Pengxia; Zhu, Yiguang; Zhang, Yuyang figshare https://doi.org/10.6084/m9.figshare.c.3637175	collection	January 2016
PlasmidSeeker: identification of known plasmids from bacterial whole genome sequencing reads Roosaare, Märt; Puustusmaa, Mikk; Möls, Märt PeerJ, Vol. 6 https://doi.org/10.7717/peerj.4588	journal	April 2018

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