Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species

Adamek M, Alanjary M, Sales-Ortells H, Goodfellow M, Bull AT, Winkler A, Wibberg D, Kalinowski J, Ziemert N (2018)
BMC GENOMICS 19: 15.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ; ;
Abstract / Bemerkung
Background: Genome mining tools have enabled us to predict biosynthetic gene clusters that might encode compounds with valuable functions for industrial and medical applications. With the continuously increasing number of genomes sequenced, we are confronted with an overwhelming number of predicted clusters. In order to guide the effective prioritization of biosynthetic gene clusters towards finding the most promising compounds, knowledge about diversity, phylogenetic relationships and distribution patterns of biosynthetic gene clusters is necessary. Results: Here, we provide a comprehensive analysis of the mode ! actinobacterial genus Amycoiatopsis and its potential for the production of secondary metabolites. A phylogenetic characterization, together with a pan-genome analysis showed that within this highly diverse genus, four major lineages could be distinguished which differed in their potential to produce secondary metabolites. Furthermore, we were able to distinguish gene cluster families whose distribution correlated with phylogeny, indicating that vertical gene transfer plays a major role in the evolution of secondary metabolite gene clusters. Still, the vast majority of the diverse biosynthetic gene clusters were derived from clusters unique to the genus, and also unique in comparison to a database of known compounds. Our study on the locations of biosynthetic gene clusters in the genomes of Amycoiatopsis' strains showed that clusters acquired by horizontal gene transfer tend to be incorporated into non conserved regions of the genome thereby allowing us to distinguish core and hypervariable regions in Amycoiatopsis genomes. Conclusions: Using a comparative genomics approach, it was possible to determine the potential of the genus Amycoiatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds.
Erscheinungsjahr
Zeitschriftentitel
BMC GENOMICS
Band
19
Art.-Nr.
15
ISSN
PUB-ID

Zitieren

Adamek M, Alanjary M, Sales-Ortells H, et al. Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species. BMC GENOMICS. 2018;19: 15.
Adamek, M., Alanjary, M., Sales-Ortells, H., Goodfellow, M., Bull, A. T., Winkler, A., Wibberg, D., et al. (2018). Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species. BMC GENOMICS, 19, 15. doi:10.1186/S12864-018-4809-4
Adamek, M., Alanjary, M., Sales-Ortells, H., Goodfellow, M., Bull, A. T., Winkler, A., Wibberg, D., Kalinowski, J., and Ziemert, N. (2018). Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species. BMC GENOMICS 19:15.
Adamek, M., et al., 2018. Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species. BMC GENOMICS, 19: 15.
M. Adamek, et al., “Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species”, BMC GENOMICS, vol. 19, 2018, : 15.
Adamek, M., Alanjary, M., Sales-Ortells, H., Goodfellow, M., Bull, A.T., Winkler, A., Wibberg, D., Kalinowski, J., Ziemert, N.: Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species. BMC GENOMICS. 19, : 15 (2018).
Adamek, Martina, Alanjary, Mohammad, Sales-Ortells, Helena, Goodfellow, Michael, Bull, Alan T., Winkler, Anika, Wibberg, Daniel, Kalinowski, Jörn, and Ziemert, Nadine. “Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species”. BMC GENOMICS 19 (2018): 15.

5 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Uncovering the potential of novel micromonosporae isolated from an extreme hyper-arid Atacama Desert soil.
Carro L, Castro JF, Razmilic V, Nouioui I, Pan C, Igual JM, Jaspars M, Goodfellow M, Bull AT, Asenjo JA, Klenk HP., Sci Rep 9(1), 2019
PMID: 30886188
Rare taxa and dark microbial matter: novel bioactive actinobacteria abound in Atacama Desert soils.
Goodfellow M, Nouioui I, Sanderson R, Xie F, Bull AT., Antonie Van Leeuwenhoek 111(8), 2018
PMID: 29721711
Revisiting the Taxonomic Status of the Biomedically and Industrially Important Genus Amycolatopsis, Using a Phylogenomic Approach.
Sangal V, Goodfellow M, Blom J, Tan GYA, Klenk HP, Sutcliffe IC., Front Microbiol 9(), 2018
PMID: 30319584
The genus Borrelia reloaded.
Margos G, Gofton A, Wibberg D, Dangel A, Marosevic D, Loh SM, Oskam C, Fingerle V., PLoS One 13(12), 2018
PMID: 30586413

81 References

Daten bereitgestellt von Europe PubMed Central.

Natural product discovery: past, present, and future.
Katz L, Baltz RH., J. Ind. Microbiol. Biotechnol. 43(2-3), 2016
PMID: 26739136
Natural Products as Sources of New Drugs from 1981 to 2014.
Newman DJ, Cragg GM., J. Nat. Prod. 79(3), 2016
PMID: 26852623
The future of antibiotics.
Spellberg B., Crit Care 18(3), 2014
PMID: 25043962
Computational approaches to natural product discovery.
Medema MH, Fischbach MA., Nat. Chem. Biol. 11(9), 2015
PMID: 26284671
The evolution of genome mining in microbes - a review.
Ziemert N, Alanjary M, Weber T., Nat Prod Rep 33(8), 2016
PMID: 27272205
The structural biology of biosynthetic megaenzymes.
Weissman KJ., Nat. Chem. Biol. 11(9), 2015
PMID: 26284673
Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.
Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian KD, Fischbach MA, Garavelli JS, Goransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Muller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJ, Rebuffat S, Ross RP, Sahl HG, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Sussmuth RD, Tagg JR, Tang GL, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA., Nat Prod Rep 30(1), 2013
PMID: 23165928
Genes and enzymes involved in bacterial isoprenoid biosynthesis.
Daum M, Herrmann S, Wilkinson B, Bechthold A., Curr Opin Chem Biol 13(2), 2009
PMID: 19318289
Gifted microbes for genome mining and natural product discovery.
Baltz RH., J. Ind. Microbiol. Biotechnol. 44(4-5), 2016
PMID: 27520548
antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters.
Weber T, Blin K, Duddela S, Krug D, Kim HU, Bruccoleri R, Lee SY, Fischbach MA, Muller R, Wohlleben W, Breitling R, Takano E, Medema MH., Nucleic Acids Res. 43(W1), 2015
PMID: 25948579
Natural products in soil microbe interactions and evolution.
Traxler MF, Kolter R., Nat Prod Rep 32(7), 2015
PMID: 26000872
Specialized microbial metabolites: functions and origins.
Davies J., J. Antibiot. 66(7), 2013
PMID: 23756686
Antibiotic-producing symbionts dynamically transition between plant pathogenicity and insect-defensive mutualism.
Florez LV, Scherlach K, Gaube P, Ross C, Sitte E, Hermes C, Rodrigues A, Hertweck C, Kaltenpoth M., Nat Commun 8(), 2017
PMID: 28452358
Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora.
Ziemert N, Lechner A, Wietz M, Millan-Aguinaga N, Chavarria KL, Jensen PR., Proc. Natl. Acad. Sci. U.S.A. 111(12), 2014
PMID: 24616526
A roadmap for natural product discovery based on large-scale genomics and metabolomics.
Doroghazi JR, Albright JC, Goering AW, Ju KS, Haines RR, Tchalukov KA, Labeda DP, Kelleher NL, Metcalf WW., Nat. Chem. Biol. 10(11), 2014
PMID: 25262415
Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters.
Cimermancic P, Medema MH, Claesen J, Kurita K, Wieland Brown LC, Mavrommatis K, Pati A, Godfrey PA, Koehrsen M, Clardy J, Birren BW, Takano E, Sali A, Linington RG, Fischbach MA., Cell 158(2), 2014
PMID: 25036635

AUTHOR UNKNOWN, 0
Amycolatopsis marina sp. nov., an actinomycete isolated from an ocean sediment.
Bian J, Li Y, Wang J, Song FH, Liu M, Dai HQ, Ren B, Gao H, Hu X, Liu ZH, Li WJ, Zhang LX., Int. J. Syst. Evol. Microbiol. 59(Pt 3), 2009
PMID: 19244425
Amycolatopsis saalfeldensis sp. nov., a novel actinomycete isolated from a medieval alum slate mine.
Carlsohn MR, Groth I, Tan GY, Schutze B, Saluz HP, Munder T, Yang J, Wink J, Goodfellow M., Int. J. Syst. Evol. Microbiol. 57(Pt 7), 2007
PMID: 17625209
Two new genera of Nocardioform Actinomycetes: Amycolata gen. nov. and Amycolatopsis gen. nov
Lechevalier MP, Prauser H, Labeda DP, Ruan J-S., 1986
Reclassification of Amycolatopsis orientalis DSM 43387 as Amycolatopsis benzoatilytica sp. nov.
Majumdar S, Prabhagaran SR, Shivaji S, Lal R., Int. J. Syst. Evol. Microbiol. 56(Pt 1), 2006
PMID: 16403887
Amycolatopsis halophila sp. nov., a halophilic actinomycete isolated from a salt lake.
Tang SK, Wang Y, Guan TW, Lee JC, Kim CJ, Li WJ., Int. J. Syst. Evol. Microbiol. 60(Pt 5), 2009
PMID: 19666809
Amycolatopsis kentuckyensis sp. nov., Amycolatopsis lexingtonensis sp. nov. and Amycolatopsis pretoriensis sp. nov., isolated from equine placentas.
Labeda DP, Donahue JM, Williams NM, Sells SF, Henton MM., Int. J. Syst. Evol. Microbiol. 53(Pt 5), 2003
PMID: 13130055
Amycolatopsis palatopharyngis sp. nov., a potentially pathogenic actinomycete isolated from a human clinical source.
Huang Y, Pasciak M, Liu Z, Xie Q, Gamian A., Int. J. Syst. Evol. Microbiol. 54(Pt 2), 2004
PMID: 15023943
Quartromicin biosynthesis: two alternative polyketide chains produced by one polyketide synthase assembly line.
He HY, Pan HX, Wu LF, Zhang BB, Chai HB, Liu W, Tang GL., Chem. Biol. 19(10), 2012
PMID: 23102224
Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis sulphurea: a platform for producing novel tetracycline antibiotics.
Lukezic T, Lesnik U, Podgorsek A, Horvat J, Polak T, Sala M, Jenko B, Raspor P, Herron PR, Hunter IS, Petkovic H., Microbiology (Reading, Engl.) 159(Pt 12), 2013
PMID: 24043447
Kigamicins, novel antitumor antibiotics. I. Taxonomy, isolation, physico-chemical properties and biological activities.
Kunimoto S, Lu J, Esumi H, Yamazaki Y, Kinoshita N, Honma Y, Hamada M, Ohsono M, Ishizuka M, Takeuchi T., J. Antibiot. 56(12), 2003
PMID: 15015727
Macrotermycins A-D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39.
Beemelmanns C, Ramadhar TR, Kim KH, Klassen JL, Cao S, Wyche TP, Hou Y, Poulsen M, Bugni TS, Currie CR, Clardy J., Org. Lett. 19(5), 2017
PMID: 28207275
BPGA- an ultra-fast pan-genome analysis pipeline.
Chaudhari NM, Gupta VK, Dutta C., Sci Rep 6(), 2016
PMID: 27071527
Mining Bacterial Genomes for Secondary Metabolite Gene Clusters.
Adamek M, Spohn M, Stegmann E, Ziemert N., Methods Mol. Biol. 1520(), 2017
PMID: 27873244
Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).
Bentley SD, Chater KF, Cerdeno-Tarraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O'Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA., Nature 417(6885), 2002
PMID: 12000953
Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis.
Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y, Hattori M, Omura S., Nat. Biotechnol. 21(5), 2003
PMID: 12692562
Natural Products and the Gene Cluster Revolution.
Jensen PR., Trends Microbiol. 24(12), 2016
PMID: 27491886
Amycolatopsis xuchangensis sp. nov. and Amycolatopsis jiguanensis sp. nov., isolated from soil.
Huang JR, Ming H, Li S, Zhao ZL, Meng XL, Zhang JX, Tang Z, Li WJ, Nie GX., Antonie Van Leeuwenhoek 109(11), 2016
PMID: 27449024
A systematic study of the whole genome sequence of Amycolatopsis methanolica strain 239T provides an insight into its physiological and taxonomic properties which correlate with its position in the genus.
Tang B, Xie F, Zhao W, Wang J, Dai S, Zheng H, Ding X, Cen X, Liu H, Yu Y, Zhou H, Zhou Y, Zhang L, Goodfellow M, Zhao GP., Synth Syst Biotechnol 1(3), 2016
PMID: 29062941
DNA-DNA hybridization values and their relationship to whole-genome sequence similarities.
Goris J, Konstantinidis KT, Klappenbach JA, Coenye T, Vandamme P, Tiedje JM., Int. J. Syst. Evol. Microbiol. 57(Pt 1), 2007
PMID: 17220447
Complete genome sequence and comparative genomic analyses of the vancomycin-producing Amycolatopsis orientalis.
Xu L, Huang H, Wei W, Zhong Y, Tang B, Yuan H, Zhu L, Huang W, Ge M, Yang S, Zheng H, Jiang W, Chen D, Zhao GP, Zhao W., BMC Genomics 15(), 2014
PMID: 24884615
Streptomyces orientalis, n. sp., the source of vancomycin.
BRIGHAM RB, PITTENGER RC., Antibiot Chemother (Northfield) 6(11), 1956
PMID: 24544146

AUTHOR UNKNOWN, 0
A proposed genus boundary for the prokaryotes based on genomic insights.
Qin QL, Xie BB, Zhang XY, Chen XL, Zhou BC, Zhou J, Oren A, Zhang YZ., J. Bacteriol. 196(12), 2014
PMID: 24706738
Proposed minimal standards for the use of genome data for the taxonomy of prokaryotes.
Chun J, Oren A, Ventosa A, Christensen H, Arahal DR, da Costa MS, Rooney AP, Yi H, Xu XW, De Meyer S, Trujillo ME., Int. J. Syst. Evol. Microbiol. 68(1), 2018
PMID: 29292687
Exploration of Amycolatopsis diversity in soil using genus-specific primers and novel selective media.
Tan GY, Ward AC, Goodfellow M., Syst. Appl. Microbiol. 29(7), 2006
PMID: 16466884
"Every Gene Is Everywhere but the Environment Selects": Global Geolocalization of Gene Sharing in Environmental Samples through Network Analysis.
Fondi M, Karkman A, Tamminen MV, Bosi E, Virta M, Fani R, Alm E, McInerney JO., Genome Biol Evol 8(5), 2016
PMID: 27190206
Comparative Genomics Reveals the Core and Accessory Genomes of Streptomyces Species.
Kim JN, Kim Y, Jeong Y, Roe JH, Kim BG, Cho BK., J. Microbiol. Biotechnol. 25(10), 2015
PMID: 26032364
Comparative Genomics Analysis of Streptomyces Species Reveals Their Adaptation to the Marine Environment and Their Diversity at the Genomic Level.
Tian X, Zhang Z, Yang T, Chen M, Li J, Chen F, Yang J, Li W, Zhang B, Zhang Z, Wu J, Zhang C, Long L, Xiao J., Front Microbiol 7(), 2016
PMID: 27446038
PGAP: pan-genomes analysis pipeline.
Zhao Y, Wu J, Yang J, Sun S, Xiao J, Yu J., Bioinformatics 28(3), 2011
PMID: 22130594
Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora.
Jensen PR, Williams PG, Oh DC, Zeigler L, Fenical W., Appl. Environ. Microbiol. 73(4), 2006
PMID: 17158611
Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism.
Zhao W, Zhong Y, Yuan H, Wang J, Zheng H, Wang Y, Cen X, Xu F, Bai J, Han X, Lu G, Zhu Y, Shao Z, Yan H, Li C, Peng N, Zhang Z, Zhang Y, Lin W, Fan Y, Qin Z, Hu Y, Zhu B, Wang S, Ding X, Zhao GP., Cell Res. 20(10), 2010
PMID: 20567260
Evolution of the terminal regions of the Streptomyces linear chromosome.
Choulet F, Aigle B, Gallois A, Mangenot S, Gerbaud C, Truong C, Francou FX, Fourrier C, Guerineau M, Decaris B, Barbe V, Pernodet JL, Leblond P., Mol. Biol. Evol. 23(12), 2006
PMID: 16956972
Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria.
Penn K, Jenkins C, Nett M, Udwary DW, Gontang EA, McGlinchey RP, Foster B, Lapidus A, Podell S, Allen EE, Moore BS, Jensen PR., ISME J 3(10), 2009
PMID: 19474814
Database Resources of the National Center for Biotechnology Information.
NCBI Resource Coordinators., Nucleic Acids Res. 45(D1), 2016
PMID: 27899561
IMG: the Integrated Microbial Genomes database and comparative analysis system.
Markowitz VM, Chen IM, Palaniappan K, Chu K, Szeto E, Grechkin Y, Ratner A, Jacob B, Huang J, Williams P, Huntemann M, Anderson I, Mavromatis K, Ivanova NN, Kyrpides NC., Nucleic Acids Res. 40(Database issue), 2012
PMID: 22194640
Genome analysis of the sugar beet pathogen Rhizoctonia solani AG2-2IIIB revealed high numbers in secreted proteins and cell wall degrading enzymes.
Wibberg D, Andersson L, Tzelepis G, Rupp O, Blom J, Jelonek L, Puhler A, Fogelqvist J, Varrelmann M, Schluter A, Dixelius C., BMC Genomics 17(), 2016
PMID: 26988094
MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S., Mol. Biol. Evol. 30(12), 2013
PMID: 24132122
FaBox: an online toolbox for fasta sequences
VILLESEN P., Mol. Ecol. Notes 7(6), 2007
PMID: IND43974552
Prokka: rapid prokaryotic genome annotation.
Seemann T., Bioinformatics 30(14), 2014
PMID: 24642063
Search and clustering orders of magnitude faster than BLAST.
Edgar RC., Bioinformatics 26(19), 2010
PMID: 20709691
JSpeciesWS: a web server for prokaryotic species circumscription based on pairwise genome comparison.
Richter M, Rossello-Mora R, Oliver Glockner F, Peplies J., Bioinformatics 32(6), 2015
PMID: 26576653
Core team: R: a language environment for statistical computing
Development R., 2008
Detecting sequence homology at the gene cluster level with MultiGeneBlast.
Medema MH, Takano E, Breitling R., Mol. Biol. Evol. 30(5), 2013
PMID: 23412913
Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database.
Carver T, Berriman M, Tivey A, Patel C, Bohme U, Barrell BG, Parkhill J, Rajandream MA., Bioinformatics 24(23), 2008
PMID: 18845581
Basic local alignment search tool.
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ., J. Mol. Biol. 215(3), 1990
PMID: 2231712
The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity.
Ziemert N, Podell S, Penn K, Badger JH, Allen E, Jensen PR., PLoS ONE 7(3), 2012
PMID: 22479523
PAST: paleontological statistics software package for education
Hammer Ø, Harper DAT, Ryan PD., 2001
Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks.
Huson DH, Scornavacca C., Syst. Biol. 61(6), 2012
PMID: 22780991

AUTHOR UNKNOWN, 0
The Pfam protein families database: towards a more sustainable future.
Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A., Nucleic Acids Res. 44(D1), 2015
PMID: 26673716
An initial strategy for comparing proteins at the domain architecture level.
Lin K, Zhu L, Zhang DY., Bioinformatics 22(17), 2006
PMID: 16837531
Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters.
Schorn MA, Alanjary MM, Aguinaldo K, Korobeynikov A, Podell S, Patin N, Lincecum T, Jensen PR, Ziemert N, Moore BS., Microbiology (Reading, Engl.) 162(12), 2016
PMID: 27902408
Biological network exploration with Cytoscape 3.
Su G, Morris JH, Demchak B, Bader GD., Curr Protoc Bioinformatics 47(), 2014
PMID: 25199793
EstimateS turns 20: statistical estimation of species richness and shared species from samples, with non-parametric extrapolation
Colwell RK, Elsensohn JE., 2014
CONTIGuator: a bacterial genomes finishing tool for structural insights on draft genomes.
Galardini M, Biondi EG, Bazzicalupo M, Mengoni A., Source Code Biol Med 6(), 2011
PMID: 21693004
Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data.
Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, Buxton S, Cooper A, Markowitz S, Duran C, Thierer T, Ashton B, Meintjes P, Drummond A., Bioinformatics 28(12), 2012
PMID: 22543367

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 29859036
PubMed | Europe PMC

Suchen in

Google Scholar