the bioinforma cs core facility in oslo - wiki.uio.no · rc for the period 2013-‐2017 (2015) na...

h�p://core.rr-‐research.no/ bioinforma�cs

The Bioinforma�cs Core Facility in Oslo

Staff:

Core facility leader Eivind Hovig


The biological data explosion The greatest challenge facing the molecular biology community today is to make sense of the wealth of data that has been produced by the genome sequencing projects – EMBL-‐EBI

Bioinforma�cs algorithms and compu�ng power are the main bo�lenecks for analyzing huge amount of data generated by the current technologies (Gálvez et al., Bioinforma�cs 26, 683 (2010)).


The biological data explosion

h�p://www.genome.gov/sequencingcosts

  Storage and processor capacity roughly double every two years (Moore’s Law)   New biological data is at present doubling every five months – rate is increasing   New sequencing machines produce billions of bases per experiment   Both users and informa�cs infrastructure have trouble adap�ng

  Very real and serious challenge for molecular biology, in Norway and elsewhere


The advantages of having a bioinforma�cs core facility

  Providing infrastructure   Broad, stable and increased competence   Cost efficient for large-‐scale projects   Help for projects of all sizes   Increase probability of a grant award  We can guide you to the correct people


Who are we?

Part of ELIXIR Norway – The Na�onal Technology Pla�orm for Bioinforma�cs

Tromsø: Nils Peder

Willassen

Bergen: Inge Jonassen

Trondheim: Finn Drabløs

Oslo: Eivind Hovig

Ås: Dag Inge Våge


ELIXIR Norway   Builds on the infrastructure and exper�se built up by the FUGE bioinforma�cs pla�orm (Funded by Research Council of Norway 2003-‐2012)

  Elixir Norway funded by the RC for the period 2013-‐2017 (2015)   Na�onal centre with nodes in Bergen, Oslo, Ås, Trondheim, and Tromsø   Offers state of the art research based infrastructure and services to Norwegian users in academia, industry, and government –  Build and offer an e-‐infrastructure for users within molecular life science –  Work �ghtly with other technology pla�orms –  Provide state of the art bioinforma�cs support –  Ensure that Norwegian data are stored in standardized formats –

suppor�ng re-‐use of data –  Work with the generic e-‐infrastructure providers to make their resources

available towards bioinforma�cs   Headed by Professor Inge Jonassen, Bergen


ELIXIR   The purpose of ELIXIR is to construct and operate a sustainable infrastructure for biological informa�on in Europe to support life science research and its transla�on to medicine and the environment, the bio-‐industries and society

  Challenges for life scien�sts in Norway and all European countries –  maintain open access to biological data to enhance compe��veness and

innova�on (free access to databases) –  manage the data deluge –  integrate the data to reduce fragmenta�on of effort and research –  exploit new types of data

  These challenges are too vast for any single ins�tu�on or country, and must therefore be managed by joining forces at European and global levels


ELIXIR

Crosswell and Thornton, Trends Biotechnol. 30, 241 (2012)


The Bioinforma�cs Core Facility in Oslo is a part of ELIXIR Norway

We are funded by   RCN – ELIXIR Norway   Helse Sør-‐Øst   User fees (Large projects only)


Who are we in Oslo? Vegard Nygaard – Microarray and sequence data analysis

Morten Johansen – Programming, scrip�ng, web servers

Marit Holden, Norsk Regnesentral – Sta�s�cal genomics

Clara-‐Cecilie Günther, Norsk Regnesentral – Sta�s�cal genomics

Eivind Hovig -‐ manager

Ståle Nygård – Sta�s�cal genomics Oslo and Na�onal Helpdesk manager

Jon K. Lærdahl – Protein structure analysis

Merete Molton Worren – High-‐throughput sequencing analysis

Daniel Vodák – HTS analysis

Torbjørn Rognes – sequence analysis

Sveinung Gundersen – Hyperbrowser Roughly 6 man-‐years of

bioinforma�cs exper�se


What do we do?

  Providing Service and Support   Access to Compu�ng Facili�es   Access to Storage  Organize and Contribute to Courses  Organize and Contribute to Conferences and Workshops


What is a bioinforma�cian?   An in�mate knowledge of UNIX-‐based opera�ng systems   Fluent in scrip�ng languages such as Perl or Python   Understanding programming languages such as C++/ C / Java, and ability to develop so�ware encapsula�ng new analysis methods   Knowledge of network-‐based data storage   Understanding of rela�onal databases and database architecture


What is a bioinforma�cian?

  Skills in sta�s�cal analysis   Understanding of experimental design   Knowledge of mathema�cal modeling

  And of course, we have a general knowledge of molecular biology and genomics


What can a bioinforma�cian do for you?   Provide the computa�onal/sta�s�cal analysis of data derived from your biological/medical experiments –  It is always be�er to be involved early in the project, before the experiments have been performed   Contribute to planning and experimental setup   Not: Here are the results/data, tell us what they mean...!

  Our knowledge and experience makes us well equipped to seek out and test novel bioinforma�cs so�ware and analysis pipelines

  We can do the programming/scrip�ng for you if you wish to do the main part of the analysis yourself


Bioinforma�cs Core Facility Helpdesk   High quality research based bioinforma�cs support   Part of the Na�onal ELIXIR Norway helpdesk   Headed by Ståle Nygård in Oslo   Common point of access: [email protected]   Or contact the experts directly – see our webpages   Have supported 100s of life science research projects the last decade   FUGE (2003-‐12) and Helse Sør-‐Øst funding

  Now exper�se from the FUGE period supplemented with new ELIXIR personnel   ELIXIR (2013-‐17) and Helse Sør-‐Øst funding


Bioinforma�cs Core Facility Helpdesk   Common point of access: [email protected]   Or contact the experts directly – see our web pages   Services within all major areas in bioinforma�cs analysis, e.g.

–  Sequence analysis –  Analysis of High-‐throughput sequencing data –  Protein structure analysis –  Analysis of DNA varia�on –  Gene�c linkage studies –  Microarrays –  General gene associa�on studies –  Sta�s�cal genomics –  Database construc�on and access –  Web services

Arranging courses and workshops

Located both at the Norwegian Radium Hospital, Montebello, and at the top floor of Ole-‐Johan Dahls hus, the new Informa�cs building at UiO

Close collabora�on with other Core Facili�es, e.g. Genomics Core Facility (GCF, Radium Hospital) and the Oslo Genotyping Core Facility


Services we provide -‐ examples


Services we provide   Analysis of high-‐throughput sequencing data

–  RNA-‐seq: expression analysis –  ChIP-‐seq: finding protein-‐DNA interac�ons – Genome sequencing: finding SNPs, indels, structural variants

–  Bisulfite: DNA methyla�on –  small-‐RNA-‐seq: Detec�ng novel noncoding RNAs, expression

– Metagenomics: Calcula�ng opera�onal taxonomic units (OTUs), crea�ng phylogene�c trees, assigning species


Services we provide   I want to visualize my data, and see where on the reference genome the (high-‐throughput) sequencing reads can be aligned   I want to see which genes are affected, and how   I want as much as possible out of my data


Services we provide -‐ examples   Discovery of germline/soma-‐�c variants   Detec�on of structural aberra�ons   Variant annota�on


Services we provide -‐ examples   Differen�al gene/transcript expression analysis

  Discovery of differen�al splicing

  Iden�fica�on of novel transcripts


Services we provide -‐ examples   Finding miRNAs expressed in colorectal cancer cells

  Tes�ng the effects of different normaliza�on methods on the data

  Checking for differen�al expression between groups

PLoS ONE 8, e66165 (2013)


Services we provide -‐ examples   Detec�ng miRNAs in the Atlan�c salmon   Novel and known expressed miRNAs

  Differen�al expression analysis between different �ssues, and between individuals infected with ISA and healthy controls

BMC Genomics 14, 482 (2013)



  Annota�on and analysis of the recently assembled cod genome

–  Cross-‐species comparison and analysis of data –  Using sequence alignment tools and annota�on

databases to iden�fy syntenic regions across species –  Using synteny informa�on to infer reliability of missing

genes/regions in newly mapped genomes

Nature 477, 207 (2011)


Services we provide – The Genomic HyperBrowser

  If you have a genomic track, we can analyse it! –  Research based service –  Genome-‐scale analysis made robust and easy –  Analyze your own data, and get custom-‐developed methodology and

tools –  Comes with >100 000 genomic tracks, 76 analyses, 42 tools –  From quick analysis to robust sta�s�cal tes�ng, in simple web

interface


The Genomic HyperBrowser   Start in your internet browser

– A public, web-‐based interface allows sophis�cated genome analysis by simple point-‐and-‐click

  If you have ques�ons, just ask –  If you need input, we can assist you directly from where you le� off

  If you need even more – We have a team of programmers and sta�s�cians that can develop novel so�ware and methodology

Nucleic Acids Res 41, W133 (2013)


The Genomic HyperBrowser -‐ examples

  Regula�on by C-‐myb transcrip�on factor –  Predict binding based on mo�fs and ENCODE data

  Promoters with methyla�on pa�ern –  Sta�s�cal evalua�on of associa�on with CpG islands

  Pathology of mul�ple sclerosis – Determine involved cell types from ENCODE data

  Map environment to genome – Vitamin D associa�on to disease through receptor

Hum Mol Genet 21, 3575 (2012)

PLoS One 7, e32281 (2012)


Services we provide   Analysis of gene sets

– Gene-‐set enrichment analysis –  Finding sta�s�cally overrepresented GO-‐terms and pathways

–  Finding related genes based on literature – Grouping together correlated genes – Mapping gene-‐lists to pathways


Services we provide   Protein structure/sequence/func�on analysis

–  Inves�gate splice variants, possible pos�ransla�onal modifica�ons, signal pep�des, and localiza�on signals by using state of the art bioinforma�cs tools

–  Iden�fy protein domains, disordered regions and predic�on of secondary structure

–  If possible, build 3D models –  Iden�fy orthologs from other species –  Phylogeny –  Iden�fy func�onally important domains/segments/

residues –  Predict effects of muta�ons or suggest residues for

site-‐directed mutagenesis


Services we provide -‐ examples   Discovered a new, 5th structural superfamily of DNA glycosylase repair enzymes

  Modelled the 3D structure – homology modelling

  Located ac�ve site and suggested residues for site-‐directed mutagenesis

  Experimental follow-‐up

HhH

H2TH

UDG AAG

Family 5 – HEAT like repeats

Nucleic Acids Res. 35, 2451 (2007)



  Generated 3D model of human bile acid receptor TGR5 (a G-‐protein coupled receptor)

  Predicted effect of muta�ons/SNPs

  Experimental follow-‐up

PLOS One 5: e12403 (2010)



Pidoux & Taskén, J. Mol. Endocrinol 44, 271 (2010) (not our work!)

Evolu�on/phylogeny of PKA cataly�c subunits Cα, Cβ, and Cγ K. Søberg, T. Jahnsen, T. Rognes, B.S. Skålhegg & J.K. Lærdahl, Plos ONE 8, e60935 (2013)


Services we provide   Sta�s�cal genomics

–  Experimental design –  Pa�ern discovery –  Clustering – Mul�variate regression –  Hierarchical inference – Mul�ple tes�ng –  Event history analysis

  Survival analysis –  Other types of analysis upon request


Services we provide -‐ examples   Integra�ve analysis of gene dosage, expression and ontology (GO) data

  Iden�fied driver genes in the carcinogenesis and chemoradioresistance of cervical cancer

  Found overrepresented biological processes including apoptosis and metabolism

PLoS Genet. 5, e1000719 (2009)


Services we provide -‐ examples   Genome-‐wide gene expression analysis of bone biopsies from pa�ents with postmenopausal osteoporosis and healthy controls, adjus�ng for age and BMI

  Found 256 transcripts confirmed for disease

J Bone Miner. Res. 26, 1793 (2011)


Services we provide   DNA and protein microarray analysis –  Design of experiment –  Image analysis –  Copy number analysis –  Genotyping analysis –  Differen�al analysis –  Classifica�on and clustering –  Survival analysis –  Meta analysis –  Quality control –  Public repository submission


Services we provide   Database and web services

–  Database access –  Provide access to local copies of selected databases –  Provide snapshot access to pa�ent data in defined formats

  Web services –  Provide access to local web services –  Maintain pointers to useful other web services

  Scrip�ng and so�ware services –  Support on scrip�ng/programming –  Support on use of Linux/Unix tools –  Help with setup of required so�ware and web-‐interfaces


Services we provide   Facilita�ng use of computa�onal resources together with USIT –  CPU: h�p://uio.no/hpc/abel –  Disk: h�ps://storebioinfo.norstore.no



End of sec�on


Helpdesk – How it works   Users contact us through e-‐mail or in person   Simple services (“less than 3 days work”) offered free of charge to Norwegian academic/government users

  Always free to ask ques�ons   Larger projects may require user fees or some form of collabora�ve research, depending on prior agreement. Any user fees will be based on a non-‐profit model and should be considered reasonable

  It is recommended to think about bioinforma�cs funding already in the planning stages of your research as this is an important and resource intensive step


Bioinforma�cs Core Facility and ELIXIR Norway Helpdesk

Our job is to help you with your bioinforma�cs needs. Please use us!


Bioinforma�cs Core Facility and ELIXIR Norway Helpdesk

A�er this course: Don’t go home to your lab and try to do everything yourself!

COLLABORATE!!


ELIXIR Norway Trondheim node – Integrated with the Bioinforma�cs Core Facility

  Located in the Laboratory Centre of St Olavs Hospital and NTNU   Focus on biomedical research, gene regula�on and large scale genomics   Helpdesk services by Bioinforma�cs Core Facility (BioCore, funded by NTNU)   Close collabora�on with Genomics Core Facility (GCF)

Finn Drabløs Professor Leader ELIXIR-‐NTNU

Pål Sætrom Professor Head BioCore

Morten Rye Researcher ELIXIR-‐NTNU

Jostein Johansen Senior Engineer Manager BioCore

Kje�l Klepper Staff Engineer ELIXIR-‐NTNU

http://www.motiflab.org


ELIXIR Norway Tromsø node -‐ SYSBIO   Located both at the Science Park and NT faculty, UiT

  Collabora�on between Dept. of Chemistry and Dept. of Informa�cs, UiT

  Focus on marine genomics/metagenomics

  Contact persons; Erik Hjerde (Help desk) Nils Peder Willassen (Head)

From le� to right: Erik Hjerde, Tim Kalkhe, Nils Peder Willassen, Edvard Pedersen, Peik Haugen, Espen Robertsen and Said Ahmed. Lars Ailo Bongo not present

ELIXIR Norway -‐ Tromsø

h�p://core.rr-‐research.no/ bioinforma�cs ELIXIR Norway -‐ Ås

ELIXIR.NO Ås node.

  Located at Centre for Integra�ve Gene�cs (CIGENE), Norwegian University of Life Sciences (UMB).

  CIGENE has established pipelines for handling large-‐scale sequencing data, with focus on de novo assembly (e.g. the Atlan�c salmon genome) and development of DNA -‐ markers (SNPs). The research is aimed at bridging the gap between genotype and phenotype in produc�on biology species.

  The primary contribu�on to ELIXIR Norway will be to make fish genomic resources and tools available to the na�onal and interna�onal research community.

  Node manager: Dag Inge Våge


ELIXIR.NO Bergen node – the Computa�onal Biology Unit

  The University of Bergen coordinates the ELIXIR Norway project and the (aspiring) Norwegian ELIXIR Node

  Bioinforma�cs at UiB organised in CBU – Computa�onal Biology Unit – including research groups and a service group

  ELIXIR Norway personnel includes programmers, service scien�sts

  Close coupling with LiceBase within Sea Lice Research Centre (SFI)

  Collabora�on with Norwegian Genomics Consor�um (NGC), PROBE (proteomics), Department of publich health (biobanks)

  Project leader: Inge Jonassen

ELIXIR Norway -‐ Bergen


Thank you!

[email protected]

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