This programs has been developed as a result of working with virologist and microbiologist who are interested in understand intra-host diversity of viruses and bacteria and their evolution on a micro-evolutionary scale. A lot of tools exist that determine the frequency of mutations (SNPs, indels) from SAM files but these have primarily been developed for diploid model organisms. DiversiTools on the other hand focuses on determining mutations from a population of haploid organisms. The large amount of sequence data provided by HTS (High-throughput sequencing) enables us to study virus and bacterial populations beyond the consensus.
To learn to use DiversiTools have a run through the different tutorials:
Papers using DiversiTools (previously btctools)
- Gömer A, Brown RJP, Pfaender S, Deterding K, Reuter G, Orton R, Seitz S, Bock CT, Cavalleri JMV, Pietschmann T, Wedemeyer H, Steinmann E, Todt D. Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance. Virus Evol. 2022 Feb 2;8(1):veac007. doi: 10.1093/ve/veac007. eCollection 2022. PubMed [citation] PMID: 35242360, PMCID: PMC8887644
- Sanders C, Veronesi E, Rajko-Nenow P, Mertens PPC, Batten C, Gubbins S, Carpenter S, Darpel K. Field-Reassortment of Bluetongue Virus Illustrates Plasticity of Virus Associated Phenotypic Traits in the Arthropod Vector and Mammalian Host In Vivo. J Virol. 2022 Jul 13;96(13):e0053122. doi: 10.1128/jvi.00531-22. Epub 2022 Jun 21. PubMed [citation] PMID: 35727032, PMCID: PMC9278112
- Dong X, Munoz-Basagoiti J, Rickett NY, Pollakis G, Paxton WA, Günther S, Kerber R, Ng LFP, Elmore MJ, Magassouba N, Carroll MW, Matthews DA, Hiscox JA. Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease. Genome Biol. 2020 Sep 7;21(1):238. doi: 10.1186/s13059-020-02148-3. PMID: 32894206; PMCID: PMC7475720.
- Clark JJ, Gilray J, Orton RJ, Baird M, Wilkie G, Filipe ADS, Johnson N, McInnes CJ, Kohl A, Biek R. Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses. PLoS Negl Trop Dis. 2020 Sep 14;14(9):e0008133. doi: 10.1371/journal.pntd.0008133. PMID: 32925939; PMCID: PMC7515184.
- López-Pérez M, Haro-Moreno JM, Coutinho FH, Martinez-Garcia M, Rodriguez-Valera F. The Evolutionary Success of the Marine Bacterium SAR11 Analyzed through a Metagenomic Perspective. mSystems. 2020 Oct 6;5(5):e00605-20. doi: 10.1128/mSystems.00605-20. PMID: 33024052; PMCID: PMC7542561.
- Pinto VB, Quadros AFF, Godinho MT, Silva JC, Alfenas-Zerbini P, Zerbini FM. Intra-host evolution of the ssDNA virus tomato severe rugose virus (ToSRV). Virus Res. 2021 Jan 15;292:198234. doi: 10.1016/j.virusres.2020.198234. Epub 2020 Nov 21. PMID: 33232784.
- Orton RJ, Wright CF, King DP, Haydon DT. Estimating viral bottleneck sizes for FMDV transmission within and between hosts and implications for the rate of viral evolution. Interface Focus. 2020 Feb 6;10(1):20190066. doi: 10.1098/rsfs.2019.0066. Epub 2019 Dec 13. PMID: 31897294; PMCID: PMC6936012.
- Rajko-Nenow P, Golender N, Bumbarov V, Brown H, Frost L, Darpel K, Tennakoon C, Flannery J, Batten C. Complete Coding Sequence of a Novel Bluetongue Virus Isolated from a Commercial Sheeppox Vaccine. Microbiol Resour Announc. 2020 Mar 5;9(10):e01539-19. doi: 10.1128/MRA.01539-19. PMID: 32139561; PMCID: PMC7171223.
- Coutinho FH, Rosselli R, Rodríguez-Valera F. Trends of Microdiversity Reveal Depth-Dependent Evolutionary Strategies of Viruses in the Mediterranean. mSystems. 2019 Nov 5;4(6). pii: e00554-19. doi: 10.1128/mSystems.00554-19. PubMed PMID: 31690594; PubMed Central PMCID: PMC6832022.
- Rajko-Nenow P, Christodoulou V, Thurston W, Ropiak HM, Savva S, Brown H, Qureshi M, Alvanitopoulos K, Gubbins S, Flannery J, Batten C. Origin of Bluetongue Virus Serotype 8 Outbreak in Cyprus, September 2016. Viruses. 2020 Jan 14;12(1). pii: E96. doi: 10.3390/v12010096. PubMed PMID: 31947695.
- Danet L, Beauclair G, Berthet M, Moratorio G, Gracias S, Tangy F, Choumet V, Jouvenet N. Midgut barriers prevent the replication and dissemination of the yellow fever vaccine in Aedes aegypti. PLoS Negl Trop Dis. 2019 Aug 14;13(8):e0007299. doi: 10.1371/journal.pntd.0007299. eCollection 2019 Aug. PubMed PMID: 31412040; PubMed Central PMCID: PMC6709925.
- Mystkowska AA, Robb C, Vidal-Melgosa S, Vanni C, Fernandez-Guerra A, Höhne M, Hehemann JH. Molecular recognition of the beta-glucans laminarin and pustulan by a SusD-like glycan-binding protein of a marine Bacteroidetes. FEBS J. 2018 Dec;285(23):4465-4481. doi: 10.1111/febs.14674. Epub 2018 Oct 28. PubMed PMID: 30300505.
- Dagleish MP, Clark JJ, Robson C, Tucker M, Orton RJ, Rocchi MS. A Fatal Case of Louping-ill in a Dog: Immunolocalization and Full Genome Sequencing of the Virus. J Comp Pathol. 2018 Nov;165:23-32. doi: 10.1016/j.jcpa.2018.09.004. Epub 2018 Oct 19. PubMed PMID: 30502792; PubMed Central PMCID: PMC6302148.
- Goldstein EJ, Harvey WT, Wilkie GS, Shepherd SJ, MacLean AR, Murcia PR, Gunson RN. Integrating patient and whole-genome sequencing data to provide insights into the epidemiology of seasonal influenza A(H3N2) viruses. Microb Genom. 2018 Jan;4(1). doi: 10.1099/mgen.0.000137. Epub 2017 Dec 21. PubMed PMID: 29310750; PubMed Central PMCID: PMC5857367.
- Milani A, Fusaro A, Bonfante F, Zamperin G, Salviato A, Mancin M, Mastrorilli E, Hughes J, Hussein HA, Hassan M, Mundt E, Terregino C, Cattoli G, Monne I. Vaccine immune pressure influences viral population complexity of avian influenza virus during infection. Vet Microbiol. 2017 May;203:88-94. doi: 10.1016/j.vetmic.2017.02.016. Epub 2017 Feb 27. PubMed PMID: 28619173.
- Khera T, Todt D, Vercauteren K, McClure CP, Verhoye L, Farhoudi A, Bhuju S, Geffers R, Baumert TF, Steinmann E, Meuleman P, Pietschmann T, Brown RJ. Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy. Antiviral Res. 2017 Mar;139:129-137. doi: 10.1016/j.antiviral.2017.01.001. Epub 2017 Jan 3. PubMed PMID: 28062191; PubMed Central PMCID: PMC5292934.
- Marathe BM, Wong SS, Vogel P, Garcia-Alcalde F, Webster RG, Webby RJ, Najera I, Govorkova EA. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice. Sci Rep. 2016 May 25;6:26742. doi: 10.1038/srep26742. PubMed PMID: 27221530; PubMed Central PMCID: PMC4879667.
- King DJ, Freimanis GL, Orton RJ, Waters RA, Haydon DT, King DP. Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus. Infect Genet Evol. 2016 Oct;44:286-292. doi: 10.1016/j.meegid.2016.07.010. Epub 2016 Jul 12. PubMed PMID: 27421209; PubMed Central PMCID: PMC5036933
- King DJ, Knowles NJ, Freimanis GL, King DP. Genome Sequencing of Foot-and-Mouth Disease Virus Type O Isolate GRE/23/94. Genome Announc. 2016 May 12;4(3). pii: e00353-16. doi: 10.1128/genomeA.00353-16. PubMed PMID: 27174269; PubMed Central PMCID: PMC4866845.
- Xia H, Beck AS, Gargili A, Forrester N, Barrett AD, Bente DA. Transstadial Transmission and Long-term Association of Crimean-Congo Hemorrhagic Fever Virus in Ticks Shapes Genome Plasticity. Sci Rep. 2016 Oct 24;6:35819. doi: 10.1038/srep35819. PubMed PMID: 27775001; PubMed Central PMCID: PMC5075774.
- Claire L. Donald , Benjamin Brennan , Stephanie L. Cumberworth , Veronica V. Rezelj, Jordan J. Clark, Marli T. Cordeiro, Rafael Freitas de Oliveira França, Lindomar J. Pena, Gavin S. Wilkie, Ana Da Silva Filipe, Christopher Davis, Joseph Hughes, Margus Varjak, Martin Selinger, Luíza Zuvanov, Ania M. Owsianka, Arvind H. Patel, John McLauchlan, Brett D. Lindenbach, Gamou Fall, Amadou A. Sall, Roman Biek, Jan Rehwinkel, Esther Schnettler, Alain Kohl. Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil. PLoS Negl Trop Dis. 2016 Oct; 10(10): e0005048. doi: 10.1371/journal.pntd.0005048.
- Michael Jacobs, Alison Rodger, David J Bell, Sanjay Bhagani, Ian Cropley, Ana Filipe, Robert J Gifford, Susan Hopkins, Joseph Hughes, Farrah Jabeen, Ingolfur Johannessen, Drosos Karageorgopoulos, Angie Lackenby, Rebecca Lester, Rebecca S N Liu, Alisdair MacConnachie, Tabitha Mahungu, Daniel Martin, Neal Marshall, Stephen Mepham, Richard Orton, Massimo Palmarini, Monika Patel, Colin Perry, S Erica Peters, Duncan Porter, David Ritchie, Neil D Ritchie, R Andrew Seaton, Vattipally B Sreenu, Kate Templeton, Simon Warren, Gavin S Wilkie, Maria Zambon, Robin Gopal, Emma C Thomson. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet. 2016 Jul 30; 388(10043): 498–503. doi: 10.1016/S0140-6736(16)30386-5.
- Fusaro A, Tassoni L, Milani A, Hughes J, Salviato A, Murcia PR, Massi P, Zamperin G, Bonfanti L, Marangon S, Cattoli G, Monne I. Unexpected Interfarm Transmission Dynamics during a Highly Pathogenic Avian Influenza Epidemic. J Virol. 2016 Jun 24;90(14):6401-11. doi: 10.1128/JVI.00538-16. Print 2016 Jul 15. PubMed PMID: 27147741; PubMed Central PMCID: PMC4936132.
- Fusaro A, Tassoni L, Hughes J, Milani A, Salviato A, Schivo A, Murcia PR, Bonfanti L, Cattoli G, Monne I. Evolutionary trajectories of two distinct avian influenza epidemics: Parallelisms and divergences. Infect Genet Evol. 2015 Aug;34:457-66. doi: 10.1016/j.meegid.2015.05.020. Epub 2015 May 20. PubMed PMID: 26003682.
- Monne I, Fusaro A, Nelson MI, Bonfanti L, Mulatti P, Hughes J, Murcia PR, Schivo A, Valastro V, Moreno A, Holmes EC, Cattoli G. Emergence of a highly pathogenic avian influenza virus from a low-pathogenic progenitor. J Virol. 2014 Apr;88(8):4375-88. doi: 10.1128/JVI.03181-13. Epub 2014 Feb 5. PubMed PMID: 24501401.
Authors and Contributors
This project is a collaboration between @rjorton and @josephhughes to enable virologists and microbiologists to understand the intra-host variation from their high-throughput reads.