III Course on Theoretical and Practical Approaches to Metagenomics and Viral Discovery

Prof. Arthur GruberAssociate Professor

Department of ParasitologyUniversity of São Paulo

Brazil

Prof. Manja MarzFull ProfessorDepartment of BioinformaticsFriedrich Schiller University Jena Germany

Date: Oct 21-25, 2019Application: send a letter of intent to argruber@usp.brApplication deadline: Oct 7Prerequisites: • Previous knowledge on Linux command line• Fundamentals on molecular virology

More information: http://bit.ly/viralbioinfo

Theoretical and practical approaches to metagenomics and viral discovery Course Description:

The advent of next-generation sequencing has brought the possibility of sequencing not only a single genome but the genomes of a whole community of microorganisms of a biome. We currently know only a small fraction of the viral diversity. The use of metagenomic data and the identification of emerging viruses represent a major challenge in terms of bioinformatics. First, viruses evolve much faster than prokaryotes and eukaryotes, leading to a higher divergence of the sequences and making their detection by conventional pairwise alignment methods more difficult. Second, the number of viral genomes available on public databases is relatively low, compared to archaea and bacteria, for instance. This aspect also makes viral sequence detection and classification much more challenging.

In this course, we intend to cover some innovative methods that have been recently developed and that can increase the sensitivity of detection of evolutionary remote viruses. One of the approaches involves the construction and application of profile HMMs. We will teach conceptual aspects of profile HMM construction, especially for taxonomically specific groups of viruses. Also, we will offer practical sessions where the students will be able to build and apply profile HMMs in metagenomic data for viral detection and discovery. We also intend to cover the fundamentals of different machine learning approaches and present in practical sessions different methods applied to viral detection, classification, virus-host interactions, among other topics.

Instructors: Prof. Manja Marz, E-mail: manja@uni-jena.de Friedrich Schiller University Jena, Germany Prof. Arthur Gruber, E-mail: argruber@usp.br Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Brazil

Schedule and location:

Oct 21 to 25, 2019 8:30 am to 12:15 pm and 13:30 to 18:00 Institute of Biomedical Sciences, Biomédicas II Building, Samuel Pessoa room – theoretical classes Institute of Biomedical Sciences, Biomédicas IV Building, room 5 – practical classes Class activities: 26 h Home activities: 4 h

Audience:

This is course is intended for graduate students, postdocs and young researchers working in the fields of metagenomics and viral discovery.

Prerequisites:

• Practical sessions will be taught using Linux servers. Previous knowledge of the Linux command line is required for the practical classes.

• The course will be taught in English. English proficiency is essential. • Fundamentals of molecular virology are also recommended.

How to register:

Please send your send your CV and a short letter of intent to Prof. Arthur Gruber (argruber@usp.br). Total number of seats: 25.

Registration deadline: October 7.

Language:

The course will be taught in English.

Official home page: http://bit.ly/viralbioinfo Content:

1. Metagenomics - challenges for viral detection and discovery 2. Profile HMM construction for viral detection discovery 3. Screening metagenomic data with profile HMMs 4. Targeted progressive assembly using profile HMMs as seeds 5. Finding proviruses in bacterial genomes using profile HMMs 6. Introduction to machine learning methods 7. SVM to detect viral miRNAs 8. Random Forrest to detect viral miRNAs 9. PCA for viral host classification 10. CNN for viral host classification 11. Introduction into RNA world 12. Folding algorithm: MacCaskill and Partition functions 13. RNAfold to determine the secondary structures of RNA viruses 14. Vienna RNA Package for the study of virus host interactions 15. LRIscan/Circos (long-range Interactions of segmented viruses) 16. Covariance models 17. Infernal to detect viral elements from (meta-)genomic samples

Bibliography:

No textbook is required for this course. Some papers covering the main topics are listed below. Additional papers will be assigned and made available on the course’s web site in advance.

Molecular virology, bioinformatics and profile HMMs

Alves, J.M., de Oliveira, A.L., Sandberg, T.O., Moreno-Gallego, J.L., de Toledo, M.A., de Moura, E.M., Oliveira, L.S., Durham, A.M., Mehnert, D.U., Zanotto, P.M., Reyes, A., and Gruber, A. (2016). GenSeed-HMM: A Tool for Progressive Assembly Using Profile HMMs as Seeds and its Application in Alpavirinae Viral Discovery from Metagenomic Data. Front Microbiol. 7, 269.

Bexfield, N., and Kellam, P. (2011). Metagenomics and the molecular identification of novel viruses. Vet J 190, 191-198.

Bibby, K., and Peccia, J. (2013). Identification of viral pathogen diversity in sewage sludge by metagenome analysis. Environ Sci Technol 47, 1945-1951.

Edwards RA, McNair K, Faust K, Raes J, Dutilh BE. (2016). Computational approaches to predict bacteriophage-host relationships. FEMS Microbiol Rev. 40, 258-272.

Fancello, L., Raoult, D., and Desnues, C. (2012). Computational tools for viral metagenomics and their application in clinical research. Virology 434, 162-174.

Grazziotin, A.L., Koonin, E.V., Kristensen, D.M. (2016). Prokaryotic Virus Orthologous Groups (pVOGs): a resource for comparative genomics and protein family annotation. Nucleic Acids Res 45(D1):D491-D498.

Huerta-Cepas, J., Szklarczyk, D., Forslund, K., Cook, H., Heller, D., Walter, M.C., Rattei, T., Mende, D.R., Sunagawa, S., Kuhn, M., Jensen, L.J., Von Mering, C., and Bork, P. (2015). eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences. Nucleic Acids Res.

Ibrahim B, Arkhipova K, Andeweg AC, Posada-Céspedes S, Enault F, Gruber A, Koonin EV, Kupczok A, Lemey P, McHardy AC, McMahon DP, Pickett BE, Robertson DL, Scheuermann RH, Zhernakova A, Zwart MP, Schönhuth A, Dutilh BE, Marz M. (2018). Bioinformatics Meets Virology: The European Virus Bioinformatics Center's Second Annual Meeting. Viruses. 10(5). pii: E256.

Kristensen, D.M., Waller, A.S., Yamada, T., Bork, P., Mushegian, A.R., and Koonin, E.V. (2013). Orthologous gene clusters and taxon signature genes for viruses of prokaryotes. J Bacteriol 195, 941-950.

Mokili, J.L., Rohwer, F., and Dutilh, B.E. (2012). Metagenomics and future perspectives in virus discovery. Curr Opin Virol 2, 63-77.

Reyes, A., Alves, J.M.P., Durham, A.M. and G ruber, A. (2017). Use of profile hidden Markov models in viral discovery: current insights. Advances in Genomics and Genetics 7 29–45

Roux, S., Enault, F., Hurwitz, B.L., and Sullivan, M.B. (2015). VirSorter: mining viral signal from microbial genomic data. PeerJ 3, e985.

Sharma, D., Priyadarshini, P., and Vrati, S. (2015). Unraveling the web of viroinformatics: computational tools and databases in virus research. J Virol 89, 1489-1501.

Skewes-Cox, P., Sharpton, T.J., Pollard, K.S., and Derisi, J.L. (2014). Profile hidden Markov models for the detection of viruses within metagenomic sequence data. PLoS One 9, e105067.

Smits, S.L., Bodewes, R., Ruiz-Gonzalez, A., Baumgartner, W., Koopmans, M.P., Osterhaus, A.D., and Schurch, A.C. (2015). Recovering full-length viral genomes from metagenomes. Front Microbiol 6, 1069.

Tang, P., and Chiu, C. (2010). Metagenomics for the discovery of novel human viruses. Future Microbiol 5, 177-189.

Yutin, N., Wolf, Y.I., Raoult, D., and Koonin, E.V. (2009). Eukaryotic large nucleo-cytoplasmic DNA viruses: clusters of orthologous genes and reconstruction of viral genome evolution. Virol J 6, 223.

Machine learning methods and virology

Lorenz, Ronny and Bernhart, Stephan H. and Höner zu Siederdissen, Christian and Tafer, Hakim and Flamm, Christoph and Stadler, Peter F. and Hofacker, Ivo L., "ViennaRNA Package 2.0", Algorithms for Molecular Biology, 6:1 26, 2011, doi:10.1186/1748-7188-6-26

Sebastian Will, Kristin Reiche, Ivo L. Hofacker, Peter F. Stadler, and Rolf

Backofen. "Inferring non-coding RNA families and classes by means of genome-scale structure-based clustering", PLoS Computational Biology, 3 no. 4, pp. e65, 2007

E. P. Nawrocki and S. R. Eddy, "Infernal 1.1: 100-fold faster RNA homology

searches", Bioinformatics 29:2933-2935, 2013 M. Fricke and M. Marz, “Prediction of conserved long-range RNA-RNA

interactions in full viral genomes,” Bioinformatics, vol. 32, p. 2928–2935, 2016.

Martin Raden, Syed M Ali, Omer S Alkhnbashi, Anke Busch, Fabrizio Costa,

Jason A Davis, Florian Eggenhofer, Rick Gelhausen, Jens Georg, Steffen Heyne, Michael Hiller, Kousik Kundu, Robert Kleinkauf, Steffen C Lott, Mostafa M Mohamed, Alexander Mattheis, Milad Miladi, Andreas S Richter, Sebastian Will, Joachim Wolff, Patrick R Wright, and Rolf Backofen, "Freiburg RNA tools: a central online resource for RNA-focused research and teaching", Nucleic Acids Research, 46(W1), W25-W29, 2018.

Chicco, D., "Ten quick tips for machine learning in computational biology."

BioData Min. 10, 35 (2017). Gökcen Eraslan, Žiga Avsec, Julien Gagneur and Fabian J. Theis, "Deep

learning: new computational modelling techniques for genomics", Nature Reviews Genetics volume 20, pages 389–40, 2019

Sam Nooij, Dennis Schmitz, Harry Vennema, Annelies Kroneman and Marion P. G. Koopmans, "Overview of Virus Metagenomic Classification Methods and Their Biological Applications", Front. Microbiol., 23 April 2018

Larrañaga P, Calvo B, Santana R, Bielza C, Galdiano J, Inza I, Lozano JA,

Armañanzas R, Santafé G, Pérez A and Robles V., "Machine learning in bioinformatics.", Briefing in Bioinformatics, 2006 Mar;7(1):86-112.

Manja Marz, Niko Beerenwinkel, Christian Drosten, Markus Fricke, Dmitrij

Frishman, Ivo L. Hofacker, Dieter Hoffmann, Martin Middendorf, Thomas Rattei, Peter F. Stadler and Armin Töpfer, "Challenges in RNA virus bioinformatics", Bioinformatics, Volume 30, Issue 13, 1 July 2014, Pages 1793–1799

INFORMATION FOR BRAZILIAN STUDENTS ONLY INFORMAÇÕES APENAS PARA ESTUDANTES BRASILEIROS

Estudantes brasileiros ou estrangeiros residentes no Brasil poderão fazer o curso de duas formas:

• Disciplina de Pós-graduação do Programa Interunidades em Bioinformática da USP

o Nesse caso os estudantes deverão solicitar sua matrícula confome instruções e formulários constantes nas páginas seguintes.

o A disciplina é a IBI 5071 - Abordagens teóricas e práticas de metagenômica para a descoberta de vírus

o A disciplina contará 2 créditos que poderão ser posteriormente transferidos ao programa de pós-graduação da origem do estudante.

o Todos os interessados devem enviar carta com justificativa para realizar a disciplina para argruber@usp.br.

o É fundamental ter conhecimento do uso de linha de comando de Linux

o O curso será oferecido inteiramente em inglês. A proficiência nesse idioma é essencial.

• Em caso de dúvidas para a matrícula, favor contactar Márcia Ferreira, secretária do Programa Interunidades de Pós-Graduação em Bioinformática. Horário de atendimento ao público - das 10-12hs e das 15-17hs. Tel. (11) 3091-9980.

• Alunos USP: Enviar ficha de matrícula (anexa) com assinatura do orientador para a Pós-Grad. da Unidade de Origem.

• Alunos externos à USP: Enviar ficha de matrícula de aluno especial (anexa), copia do RG, CPF, Diploma de Graduação (ou certificado de colação de grau) e Histórico Escolar - para cpgbio@ime.usp.br

• Curso de livre Cultura e Extensão da USP na modalidade Atualização

o Nesse caso o estudante deverá solicitar inscrição através do sistema Apolo da USP pelo endereço https://uspdigital.usp.br/apolo/ ou diretamente pelo link http://bit.ly/2kvId8o.

o O prazo de inscrição é 5 de outubro de 2019

o Ao final do curso serão distribuídos certificados oficiais gerados pela Universidade

o Todos os interessados devem enviar carta com justificativa para realizar a disciplina para argruber@usp.br.

o É fundamental ter conhecimento do uso de linha de comando de Linux

o O curso será oferecido inteiramente em inglês. A proficiência nesse idioma é essencial.

IBI 5071 - ABORDAGENS TEÓRICAS E PRÁTICAS DE METAGENÔMICA PARA A DESCOBERTA DE VÍRUS

Ministrantes:

· Profa. MANUELA MARZ (MANJA MARZ), da Friedrich Schiller University Jena, Alemanha (https://www.rna.uni-jena.de/members/manja-marz/)

· Prof. ARTHUR GRUBER, ICB, USP, Brasil

Responsável: Prof. Arthur Gruber Idioma: A disciplina será inteiramente oferecida em inglês Créditos: 02 Período: 21 a 25 de outubro de 2019 Horário: 08h30 às 12h00 e das 13h30 às 18h00, de Segunda a Sexta-feira Local: Instituto de Ciências Biomédicas, Edifícios Biomédicas 2 (aulas

teóricas) e 4 (aulas práticas) Conteúdo: Conceitos e uso de ferramentas para a construção e aplicação de

HMMs de perfil (AG) e de técnicas de aprendizado de máquina (MM) para a detecção, classificação e descoberta de vírus

Inscrições:

· Todos os interessados devem enviar carta com justificativa para realizar a disciplina para argruber@usp.br.

• É fundamental ter conhecimento do uso de linha de comando de Linux

• O curso será oferecido inteiramente em inglês. A proficiência nesse idioma é essencial.

· Alunos USP: Enviar ficha de matrícula (anexa) com assinatura do

orientador para a Pós-Grad. da Unidade de Origem · Alunos externos à USP: Enviar ficha de matrícula de aluno especial

(anexa), copia do RG, CPF, Diploma de Graduação (ou certificado de colação de grau) e Histórico Escolar - para cpgbio@ime.usp.br

Requerimento de Matrícula Interunidades em Bioinformática

Nome: ____________________________________________________________ Primeira Matrícula na USP ( ) Sim ( ) Não Número Janus: ___________________ Código Nome da Disciplina Status

Uso ( ) Excedente ( )*

Uso ( ) Excedente ( )*

Uso ( ) Excedente ( )*

Uso ( ) Excedente ( )*

Uso ( ) Excedente ( )*

* Somente será possível quando já tiver concluído os créditos exigidos e feito a qualificação. São Paulo, _______ de _________________de _______. ______________________________ Assinatura do(a) Candidato(a) De acordo: SP, _____/______/______ ___________________________________ Assinatura do(a) Orientador(a)

Requerimento de Matrícula Interunidades em Bioinformática

Aluno especial - _____ sem/2_____ Nome: ____________________________________________________________

Já solicitou matrícula como aluno especial anteriormente ( ) Sim ( ) Não

Autorização do ministrante

Código Nome da Disciplina

São Paulo, _______ de _________________de _______.

______________________________

Assinatura do(a) Candidato(a)

Endereço:________________________________________________________ Cidade: ________________________cep: ________________tel: ___________ Local de Trabalho (endereço)________________________________________ Cep:____________ Tel:___________________________ Endereço eletrônico:______________________________________________

Entregar esse formulário na secretaria junto com os documentos: RG, CPF, Diploma de Graduação e Histórico Escolar