eRapport

The Helse Sør-Øst Microarray Core Facility

Prosjekt
Prosjektnummer
2010119
Ansvarlig person
Leonardo A. Zepeda Meza
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Regional teknologisk kjernefasilitet
Helsekategori
Cancer
Forskningsaktivitet
1. Underpinning
Rapporter
2012 - sluttrapport
The Helse Sør-Øst Genomics Core Facility, previously know as the Microarray Core Facility, has provided state-of-the-art high-throughput genomics services to study genome structure, dynamics and function. This has been achieved by building up scientific competence and easy access to the latest advanced technology and equipment. The Core Facility offers a wide repertoire of genomics services to analyse the genome, transcriptome and epigenome, and is an Illumina certified service provider for beadarray and high-throughput sequencing applications, assuring the highest level of quality for our services. During the project period, 2009-2012, we have fulfilled all our objectives and goals. A number of new technologies and protocols have been implemented and now offered as routine services, including sequencing and analysis of the transcriptome by RNA-Seq, as well as protocols to study DNA-protein interactions (ChIP-Seq). In addition to our original objectives, we have also established additional protocols for quantification and discovery of small RNA by sequencing, and targeted resequencing for identification of somatic mutations. New protocols are constantly being adopted. The corresponding analysis pipelines have been also implemented for the established analyses, as well as a secure IT infrastructure for handling patient sensitive sequencing data (Collaboration with UiO, Bioinformatics Core Facility, Center for Cancer Biomedicine). More information at oslo.genomics.no The Genomics Core Facility has contributed to a large number of scientific project, many of them contributing to innovation. As a policy, the Core Facility does not request authorship or ownership for the services provided and has not been directly involved in innovation. A list of our own publication is included. In addition, a number of our services have contributed to the identification of novel candidate biomarkers associated with disease, as well as new molecular signatures. A subset of these candidate biomarkers are currently being investigated further and validated in extended panels of samples. The Genomics Core Facility will be leading the sequencing technology development for large-scale genome-based diagnostics for cancer therapy decisions. This project has the potential of dramatically changing cancer treatment, targeting tumours based on their genetic makeup. Two large grants from the Research Council of Norway have been granted to the consortium to sequence many hundreds of tumours and their matching normal. This project has recently started. Overall, the Genomics Core Facility through it services has contributed to the national and international competiveness of many research groups in Helse Sør-Øst.
2011
A national competence centre and service provider for high-throughput genomics. The Helse Sør-Øst Microarray and Sequencing Core facility located at the Oslo University Hospital has for over 12 years provided the Norwegian researchers state-of-the-art high-throughput genome analysis services to study the genome structure, function and activity.The Microarray and Sequencing Core facility (MSCF) aims to contribute to the international competitiveness of scientists by providing easy access to the latest technologies and cutting-edge scientific competence on high-throughput genomic analysis. The MSCF specializes on medical and cancer-related projects, and is a co-founder of the Norwegian Cancer Genomics Consortium (cancergenomics.no) where it will be responsible of providing the sequencing technology for large-scale genome-based diagnostics for cancer therapy decisions. Comprehensive service solutions The MSCF offers a wide-range of services using different commercial microarray platforms, including Affymetrix, Agilent, Illumina and Nimblegen, as well as high-throughput sequencing services using Illumina technology. The core facility has successfully gone through a certification process to become an Illumina CSPro certified service provider for microarray technology, the second such facility in Europe, and more recently for high-throughput sequencing applications, the second facility in the Nordic region. The certification is an assurance of the level and quality of our services. Each project starts with a free advisory meeting, where the MSCF scientific and bioinformatic team presents the relevant laboratory and bioinformatic services. Based on the advisory meeting, a service agreement is generated. All incoming samples are quality-controlled and processed according to high standards. A detailed report is generated at the end of the service. Additional custom bioinformatic analysis can be contracted upon request. Services available Gene expression profiling - mRNA and miRNA profiling using catalogue and custom expression microarrays - Transcriptome sequencing (RNA-Seq) and small RNA-Seq for quantification and discovery Genomic profiling - DNA copy number analysis using commercial oligonucleotides and SNP microarrays - Genomic sequencing using paired-end and mate pair approaches for indels, translocations and DNA copy number changes - Targeted resequencing applications for exome, kinome and custom Epigenetic profiling - DNA methylation profiling using Illumina’s Infinium beadarray technology - Chromatin immunoprecipitation couple with microarrays (ChIP-Chip) or sequencing (ChIP-Seq) to study histone modifications, DNA methylation DNA and transcription factor binding Bioinformatic analysis Users can choose from different levels of data analyses, from generation of gene lists to biochemical pathway analysis. Advanced analyses are provided in collaboration with the Bioinformatic core facility. Courses The MSCF organises different courses - Introduction to High-throughput Genomic Analysis - J-Express Data Analysis Course for hands-on training in microarray data analysis - Introduction to Analysis of Next Generation Sequencing Data for hands-on training on mapping, annotation, statistical analysis and visualisation of high-throughput sequencing data (small RNA-Seq, RNA-Seq and ChIP-Seq). Short overview of users Since January 2010 the MSCF has performed 95 services for a total cost of approx. 5.4 MNOK. Approx. 75% of the services were for HSØ users. The MSCF will continue to develop and expand the capacity for expression and genomic profiling services as a cost-effective method of producing high-quality data, servicing regional customers, as well as increase the capacity to perform advanced data analysis. For more information please visit www.medicalgenomics.no.
2010
Helse Sør-Øst og Universitetet i Oslos Mikromatrise- og Sekvenseringskjernefasilitet (MSKF) tilbyr det aller siste innen laboratorieteknologi og høykapasitets genomiske metoder til det vitenskaplige miljøet i Norge for å studere genomers struktur og funksjon.Mikromatriseteknologi omfatter en rekke metoder hvor tusenvis av probemolekyler er plassert med høy tetthet på en overflate, og kan brukes til å måle mengden av komplementære molekyler i en kompleks løsning. Dette gjør at man parallelt kan måle tusenvis av molekylære interaksjoner, og metodene blir brukt til å forstå hvordan biologiske systemer reagerer på for eksempel kjemisk behandling, miljøendringer eller onkogene signaler. Høykapasitets sekvenseringsteknologi har blitt utviklet til et massivt parallelt matriseformat, og den nye generasjonen av sekvenseringsmaskiner kan bestemme milliarder av basepar, for eksempel et komplett genom på få dager. Teknologien revolusjonerer forskningen med sin enkeltbase-oppløsning og kvantitative måling. Med den nyeste teknologien innen høykapasitets sekvensering kan vi tilby protokoller for å studere genomvariasjon, genekspresjon og epigenetikk. Disse komplekse teknologiene krever dyrt og spesialisert utstyr, og høyt kvalifisert arbeidskraft. MSKF har i lang tid tilbudt denne typen infrastruktur og laboratorie- og bioinformatisk ekspertise til forskere i feltet, med svært positive evalueringer, både fra NFR/FUGEs internasjonale komité og våre brukere. Mål • Kunne tilby det nyeste innen høykapasitets-genomiske metoder til norske og utenlandske brukere, og slik bidra til deres internasjonale konkurransedyktighet. • Ha høy vitenskaplig kompetanse på bruk av den nyeste teknologien for genstruktur og –funksjonsanalyser. Teknologi og service MSKF tilbyr en rekke mikromatriseplattformer, inkludert Affymetrix-, Agilent-, Illumina- og Nimblegen- teknologi. Kjernefasiliteten ble som den andre fasiliteten i Europa Illumina CSPro sertifisert for genekspresjon i 2008, og gjennomgår for øyeblikket en sertifiseringsprosess for høykapasitetsekvensering. MSKF tilbyr: • mRNA og miRNA ekspresjonsanalyser på kommersielle mikromatriseplattformer og sekvensering. Vi tilbyr standard mikromatriser, i tillegg til spesiallagede Nimblegen og Agilent mikromatriser for ikke-standariserte arter. • DNA kopiantall profileringsanalyser for studie av vanlige DNA kopiantallsforandringer ved sykdom, og normal kopiantallsvariasjon. • Epigenetiske profileringsanalyser. MSKF bruker Illuminas Infinium teknologi, med DNA metyleringsanalyser som dekker hele genomet. I tilegg har vi etablert kromatin immunopresipitering og mikromatriser, og immunopresipitering og sekvensering for kromatinstruktur og transkripsjonsfaktor-bindingsanalyser. • Dataanalysetjenester med analyseprotokoller for blant annet ulike nivå av genekspresjonsanalyser, DNA kopiantall- og CpG-øy metyleringsanalyser. Beskrivelse av våre tjenester MSKF tilbyr ulike nivåer på tjenestene, fra full eksperimentell service hvor brukeren leverer RNA- eller DNA-prøvene og mottar enten rådata eller normaliserte data, til bioinformatiske analyser som inkluderer generering av genlister, ontologi analyser og reaksjonsveier. Hvert prosjekt starter med et gratis rådgivingsmøte, hvor brukeren forklarer den vitenskaplige bakgrunnen og målet med prosjektet. Sammen med brukeren blir man enige om eksperimentelt oppsett, hvilken teknologi som skal benyttes, hvilke dataanalyser som skal utføres og tidsskjema. Brukeren mottar en skriftlig rapport etter avsluttet analyse. Mer informasjon finnes på core.ous-research.no/microarray eller microarray.no. MSKF er en del av Norsk Mikromatrisekonsortium (NMC).
Vitenskapelige artikler
Kresse Stine H, Meza-Zepeda Leonardo A, Machado Isidro, Llombart-Bosch Antonio, Myklebost Ola

Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations.

Cancer 2012 Jan;118(2):558-70. Epub 2011 jun 28

PMID: 21713766

Skårn Magne, Namløs Heidi M, Noordhuis Paul, Wang Meng-Yu, Meza-Zepeda Leonardo A, Myklebost Ola

Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222.

Stem Cells Dev 2012 Apr;21(6):873-83. Epub 2011 aug 24

PMID: 21756067

Kuijjer Marieke L, Rydbeck Halfdan, Kresse Stine H, Buddingh Emilie P, Lid Ana B, Roelofs Helene, Bürger Horst, Myklebost Ola, Hogendoorn Pancras C W, Meza-Zepeda Leonardo A, Cleton-Jansen Anne-Marie

Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data.

Genes Chromosomes Cancer 2012 Jul;51(7):696-706. Epub 2012 mar 27

PMID: 22454324

Chymkowitch Pierre, Eldholm Vegard, Lorenz Susanne, Zimmermann Christine, Lindvall Jessica M, Bjørås Magnar, Meza-Zepeda Leonardo A, Enserink Jorrit M

Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes.

Proc Natl Acad Sci U S A 2012 Jun;109(26):10450-5. Epub 2012 jun 11

PMID: 22689984

Reikvam Dag Henrik, Derrien Muriel, Islam Rejoanoul, Erofeev Alexander, Grcic Vedrana, Sandvik Anders, Gaustad Peter, Meza-Zepeda Leonardo A, Jahnsen Frode L, Smidt Hauke, Johansen Finn-Eirik

Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice.

Eur J Immunol 2012 Nov;42(11):2959-70. Epub 2012 sep 4

PMID: 22865203

Namløs Heidi M, Meza-Zepeda Leonardo A, Barøy Tale, Østensen Ingrid H G, Kresse Stine H, Kuijjer Marieke L, Serra Massimo, Bürger Horst, Cleton-Jansen Anne-Marie, Myklebost Ola

Modulation of the osteosarcoma expression phenotype by microRNAs.

PLoS One 2012;7(10):e48086. Epub 2012 okt 25

PMID: 23133552

Kresse Stine H, Rydbeck Halfdan, Skårn Magne, Namløs Heidi M, Barragan-Polania Ana H, Cleton-Jansen Anne-Marie, Serra Massimo, Liestøl Knut, Hogendoorn Pancras C W, Hovig Eivind, Myklebost Ola, Meza-Zepeda Leonardo A

Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

PLoS One 2012;7(11):e48262. Epub 2012 nov 7

PMID: 23144859

Bjørnstad Linn G, Meza Trine J, Otterlei Marit, Olafsrud Solveig M, Meza-Zepeda Leonardo A, Falnes Pål Ø

Human ALKBH4 interacts with proteins associated with transcription.

PLoS One 2012;7(11):e49045. Epub 2012 nov 8

PMID: 23145062

Skotheim Rolf I, Meza-Zepeda Leonardo A, Hovig Eivind, Lønning Per E, Lothe Ragnhild A, Myklebost Ola

[Genome sequencing for personalized cancer treatment].

Tidsskr Nor Laegeforen 2012 Nov;132(21):2406-8.

PMID: 23160594

Ohnstad Hege O, Castro Russell, Sun Jinchang, Heintz Karen-Marie, Vassilev Lyubomir T, Bjerkehagen Bodil, Kresse Stine H, Meza-Zepeda Leonardo A, Myklebost Ola

Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma.

Cancer 2013 Mar 1;119(5):1013-22. Epub 2012 nov 16

PMID: 23165797

Reikvam Dag Henrik, Erofeev Alexander, Sandvik Anders, Grcic Vedrana, Jahnsen Frode Lars, Gaustad Peter, McCoy Kathy D, Macpherson Andrew J, Meza-Zepeda Leonardo A, Johansen Finn-Eirik

Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression.

PLoS One 2011;6(3):e17996. Epub 2011 mar 21

PMID: 21445311

Dahlback Hanne-Sofie S, Brandal Petter, Krossnes Bård K, Fric Radek, Meling Torstein R, Meza-Zepeda Leonardo A, Danielsen Håvard E, Heim Sverre

Multiple chromosomal monosomies are characteristic of giant cell ependymoma.

Hum Pathol 2011 Dec;42(12):2042-6. Epub 2011 jun 17

PMID: 21683982

Kuijjer Marieke L, Namløs Heidi M, Hauben Esther I, Machado Isidro, Kresse Stine H, Serra Massimo, Llombart-Bosch Antonio, Hogendoorn Pancras C W, Meza-Zepeda Leonardo A, Myklebost Ola, Cleton-Jansen Anne-Marie

mRNA expression profiles of primary high-grade central osteosarcoma are preserved in cell lines and xenografts.

BMC Med Genomics 2011;4():66. Epub 2011 sep 20

PMID: 21933437

Hjortland Geir Olav, Meza-Zepeda Leonardo A, Beiske Klaus, Ree Anne H, Tveito Siri, Hoifodt Hanne, Bohler Per J, Hole Knut H, Myklebost Ola, Fodstad Oystein, Smeland Sigbjorn, Hovig Eivind

Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma.

BMC Cancer 2011;11():455. Epub 2011 okt 20

PMID: 22014070

Ottaviano Laura, Schaefer Karl-Ludwig, Gajewski Melanie, Huckenbeck Wolfgang, Baldus Stefan, Rogel Uwe, Mackintosh Carlos, de Alava Enrique, Myklebost Ola, Kresse Stine H, Meza-Zepeda Leonardo A, Serra Massimo, Cleton-Jansen Anne-Marie, Hogendoorn Pancras C W, Buerger Horst, Aigner Thomas, Gabbert Helmut E, Poremba Christopher

Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort.

Genes Chromosomes Cancer 2010 Jan;49(1):40-51.

PMID: 19787792

Eide Marianne Brodtkorb, Liestøl Knut, Lingjaerde Ole Christian, Hystad Marit E, Kresse Stine H, Meza-Zepeda Leonardo, Myklebost Ola, Trøen Gunhild, Aamot Hege Vangstein, Holte Harald, Smeland Erlend Bremertun, Delabie Jan

Genomic alterations reveal potential for higher grade transformation in follicular lymphoma and confirm parallel evolution of tumor cell clones.

Blood 2010 Sep;116(9):1489-97. Epub 2010 mai 26

PMID: 20505157

Henriksen Jørn, Stabell Marianne, Meza-Zepeda Leonardo A, Lauvrak Silje Au, Kassem Moustapha, Myklebost Ola

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells.

BMC Cancer 2010;10():329. Epub 2010 jun 25

PMID: 20576167

Kresse Stine H, Szuhai Karoly, Barragan-Polania Ana H, Rydbeck Halfdan, Cleton-Jansen Anne-Marie, Myklebost Ola, Meza-Zepeda Leonardo A

Evaluation of high-resolution microarray platforms for genomic profiling of bone tumours.

BMC Res Notes 2010;3():223. Epub 2010 aug 8

PMID: 20691109

Kresse Stine H, Ohnstad Hege O, Bjerkehagen Bodil, Myklebost Ola, Meza-Zepeda Leonardo A

DNA copy number changes in human malignant fibrous histiocytomas by array comparative genomic hybridisation.

PLoS One 2010;5(11):e15378. Epub 2010 nov 9

PMID: 21085701

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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