Bio-IT World & Cambridge Healthtech Institute’s Fifth ... · Genome Informatics Sequencing Informatics Europe Clinical Genomics ... Challenging translational Bottlenecks Manon van

Organized by Cambridge Healthtech Institute

Clinical Exome SequencingRNA-Seq and Transcriptome Analysis

ClinicalGenomicsInformatics.com

High-Scale ComputingGenome Informatics

Sequencing Informatics

EuropeClinical Genomics & Informatics

Bio-IT World & Cambridge Healthtech Institute’s Fifth International

4-6 December 2013 • Sheraton Hotel & Spa • Lisbon, Portugal

Pre-ConferenCe SymPoSIa:Clinical Epigenetics Digital Detection

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Final Agenda

Anne Cambon-Thomsen, M.D., Centre National de la Recherche Scientifique (CNRS)

Niklas Blomberg, Ph.D., ELIXIR Hub, EMBL-EBI

Timothy Hubbard, Ph.D., Wellcome Trust Sanger Institute

Hans-Hilger Ropers, M. D., Ph.D., Humboldt University and Max Planck Institute for Molecular Genetics

Keynote SPeaKerS:

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Tuesday, 3 December Wednesday, 4 December Thursday, 5 December Friday, 6 December

AMClinical Epigenetics

Symposium

Sequencing Stream: Clinical Exome Sequencing

Sequencing Stream: Clinical Exome Sequencing

Sequencing Stream: RNA-Seq and Transcriptome Analysis

PM Sequencing Stream: Clinical Exome Sequencing



AM Quantitative Digital Detection

Technologies Symposium

Informatics Stream: High-Scale Computing

Informatics Stream: High-Scale Computing Informatics Stream: Genome Informatics

PM Informatics Stream: High-Scale Computing Informatics Stream: Genome Informatics Informatics Stream: Genome Informatics

Conference-at-a-Glance

about the eventBio-IT World and Cambridge Healthtech Institute are proud to announce the Fifth International Clinical Genomics & Informatics europe conference. This year’s meeting will be held 4-6 December 2013 in Lisbon, Portugal. The conference will feature four main tracks on Clinical Exome Sequencing, High-Scale Computing, Genome Informatics, and RNA-Seq and Transcriptome Analysis. In addition, we will be featuring two pre-conference Symposia on Tuesday, 3 December on Clinical Epigenetics and Quantitative Digital Detection Technologies.

The conference will tackle the huge amounts of sequencing data produced by new technologies that have introduced significant challenges for bioinformatics, both in terms of the analysis and interpretation of data and clinical implementation of novel variants. Members of the international community will come together to look at the science and informatics required to utilize next-generation sequencing for the molecular diagnosis of complex diseases.

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CLINICALINFORMATICSNEWS

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Sponsorship & exhibit opportunitiesCHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space and branding, as well as the use of the pre and post-show delegate lists. Customizable sponsorship packages allow you to achieve your objectives before, during, and long after the event. Signing on early will allow you to maximize exposure to qualified decision-makers!

agenda PresentationsShowcase your solutions to a guaranteed, highly-targeted audience. Package includes a 15 or 30-minute podium presentation within the scientific agenda, exhibit space, on-site branding, and access to cooperative marketing efforts by CHI.

Breakfast & Luncheon PresentationsOpportunity includes a 30-minute podium presentation over breakfast or lunch in the main session room. A limited number of presentations are available for sponsorship and they will sell out quickly. Sign on early to secure your talk!

Invitation-only VIP Dinner/Hospitality SuiteSponsors will select their top prospects from the conference pre-registration list for an evening of networking at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects. Evening will be customized according to sponsor’s objectives:

• Purely social• Focus group• Reception style • Plated dinner with specific conversation focus

exhibitExhibitors will enjoy facilitated networking opportunities with highly-targeted delegates making it the perfect opportunity to speak face-to-face with prospective clients and showcase your latest product, service, or solution.

Exhibit booth comes pre-fabricated with back and side panels, 1 table, 2 stools, 4 spotlights, and 1 electrical connection.

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Hotel & travel InformationConference Venue & Hotel:Sheraton Lisboa Hotel & Spa Rua Latino Coelho No 1 1069-025 Lisboa, Portugal +351-21-312-0000

Please visit www.ClinicalGenomicsInformatics.com to reserve your sleeping accommodations or call the Hotel directly. You will need to identify yourself as a Cambridge Healthtech conference attendee to receive the discounted room rate with the Host Hotel. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space- and rate-availability basis. Rooms are limited, so please book early.

flights: If you need help booking airfare please contact our dedicated travel agent, Rona Meizler, at +1 617-559-3735 or [email protected].

Discounted room rate: €120 Single/€140 Double **Includes Breakfast**

Discounted room rate Cut-off Date: 5 november 2013

top reasons to book at the Sheraton Hotel & Spa• Breakfast is included in the room rate.• No commute! The conference is taking place in the hotel.• Ultra modern Spirito Spa & Fitness Center, outdoor heated pool & Mediterranean spa services.

• Located just minutes from the city’s downtown Baxia, where you can admire Augusta Street, Russio and Commercio Square (shopping, galleries & theaters).

• 15 minutes from Lisbon’s Portela International Airport.• Minutes from local attractions like Avenida da Liberdade, Praca do Comercio (magnificent Square by the River), Estrelas Basilicia, and Belem Tower to name a few.

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Pre-Conference Symposium: Clinical epigenetics08:30 registration and morning Coffee

09:00 Chairperson’s opening remarks

UNDERLYING MECHANISMS LEADING TO DISEASE09:10 Promoter methylation in Colorectal Cancer: Promising Clinical applications, Challenging translational BottlenecksManon van Engeland, Ph.D., Professor, Department of Pathology, School for Oncology and Developmental Biology, Maastricht University Medical Center, The NetherlandsThe epigenetic background of CRC is being unraveled rapidly. First, I will briefly review the latest data on the CRC methylome. Next, I will present the clinical relevance of methylation markers for early detection of CRC and prediction of prognosis and response to therapy in CRC. Finally, I will discuss the challenges in bringing these markers to the clinic.

09:40 Dna methylation and Demethylation in Health and DiseaseFrançois Fuks, Ph.D., Director, Laboratory of Cancer Epigenetics, Faculty of Medicine, Free University of Brussels, BelgiumA host of new actors and novel cytosine modifications and the ten eleven translocation (TET) enzymes have appeared on the scene, sparking great interest. The challenge is now to uncover the roles they play and how they relate to DNA demethylation. Knowledge is accumulating linking these new players to essential biological processes (e.g. cell pluripotency and development) and also to cancerogenesis. We will present data highlighting new modes of action of TETs and their roles in diseases.

10:10 Long noncoding rnas and the Specification of epigenetic modifications in Development and DiseaseMarcel Dinger, Ph.D., Head, Clinical Genomics, Centre for Clinical Genomics, Garvan Institute of Medical Research, AustraliaAlthough the mechanisms and protein complexes that enact such epigenetic modifications are known, it remains a mystery how these chromatin-modifying factors, which seldom possess any sequence-specificity per se, are directed with such remarkable specificity to particular sites of the genome. In this presentation, I will present evidence to support the case that long non-coding RNAs may fulfill a fundamental role in directing generic chromatin-modifying machinery to particular sites in the genome.

10:40 Coffee Break

UTILIZATION OF EPIGENETIC BIOMARKERS IN CLINICAL MANAGEMENT

11:10 Dna methylation Biomarkers for early Detection and monitoring of CancerGuro Elisabeth Lind, Ph.D., Head, Epigenetics, Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, NorwayA panel of methylated biomarkers suitable for detecting colorectal cancer at an early stage will be presented. In tissue samples, this panel outperforms several previously published epi-markers, including VIM and SEPT9 which are included in current non-invasive colorectal cancer tests. We are also working with urological cancers, lymphomas and cholangiocarcinomas and some of our latest data for early detection and/or monitoring of these diseases will be presented.

11:40 the epigenetic and Genetic Context of mGmt Promoter methylation and Its Impact on the Predictive versus Prognostic Value as a Biomarker for GliomaMonika E. Hegi, Ph.D., Head, Laboratory of Tumor Biology & Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois (CHUV), SwitzerlandThe presentation will review the predictive value of MGMT promoter methylation in glioblastoma (glioma, WHO grade IV) for benefit from alkylating agent therapy. This is a mechanistically plausible relationship due to the DNA repair function of MGMT that removes the most cytotoxic lesion introduced by alkylating agents. Surprisingly, a strong prognostic effect was observed for MGMT methylation in clinical trials with grade III glioma. The genetic and epigenetic context of this surprising, and clinically relevant difference will be discussed.

12:10 Sponsored Presentation (Sponsorship Opportunity Available)

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on your own

13:10 Session Break


DISCOVERY OF EPIGENETIC MARKERS FOR DIAGNOSTIC & PROGNOSTIC UTILITY14:05 Dynamic Changes in 5-Hydroxymethylation (5hmC) Signatures Underpin early and Late events in Drug exposed LiverRichard Meehan, Ph.D., Senior Scientist, Chromosomes and Gene Expression, Medical Research Council, The Human Genetics Unit (HGU), Western General Hospital, United KingdomCombined epigenomic and transcriptomic approaches can identify sets of potential biomarkers for disease progression, including cancer. Our work demonstrates that 5hmC profiling can be used as a unique indicator of cell states during organ maturation and drug-induced responses. 5hmC profiling provides novel epigenetic signatures for integrated pathway analysis and is the foundation for the epigenetics of identity.

14:35 Genome-Wide methylation analysis on neuroendocrine tumorsChristina Thirlwell, Ph.D., Senior Lecturer & Medical Oncologist, University College London, United KingdomMy group has undertaken the first large scale integrated genomic analysis of pancreatic and intestinal NETs including exome sequencing, genome-wide DNA methylation analysis, RNA expression and copy number analysis. DNA methylation biomarkers have been identified which differentiate between normal tissue and NETs and also between histological grade of NET. Most recently we have isolated and sequenced DNA from single NET circulating tumor cells (CTCs). Analysis of this “liquid biopsy” will in the future enable us to truly personalize cancer therapy for NET patients.

15:05 Genetic Disruption of epigenetic enzymes in Human Disorders: Impact in Clinical managementMaría Berdasco Menéndez, Ph.D., Associate Researcher, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)Deregulation of epigenetic profiles has been described in several human pathologies, including complex diseases (such as cancer, cardiovascular and neurological diseases), metabolic pathologies (type 2 diabetes or obesity) and a great number of rare disorders. Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanisms are linked to such epigenetic deregulation. We will describe some germline mutations of epigenetic modifiers that are known to be associated with human disorders (mainly cancer), and discuss their translational potential as cancer biomarkers or their impact in therapeutic strategies.

15:35 refreshment Break

16:10 Dna methylation in Childhood CancerKeith Brown, Ph.D., Reader, Molecular Pathology, School of Cellular & Molecular Medicine, University of Bristol, United KingdomWe have used genome-wide DNA methylation analysis to identify epigenetic alterations in clinically important childhood cancers, specifically Wilms’ tumor of the kidney and neuroblastoma, a cancer of the sympathetic nervous system. We have identified the first example of long-range epigenetic silencing in childhood cancer, as well as novel single genes that are silenced by DNA methylation. Analyzes of clinically annotated patient cohorts are being used to test the diagnostic and prognostic utility of these markers.

16:35 Dna methylation Signatures for Prediction of Biochemical recurrence after radical Prostatectomy of Clinically Localized Prostate CancerChrista Haldrup, Ph.D., Research Scientist, Department of Molecular Medicine, Aarhus University Hospital, DenmarkThrough screening of prostate cancer samples and samples of adjacent normal prostate tissue, we here identify six genes (AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B) which are hypermethylated in prostate cancer. Furthermore, DNA methylation of C1orf114 is significantly associated with time to PSA recurrence in multivariate cox regression analysis encompassing standard histopathological parameters in two international radical prostatectomy cohorts. Additionally we develop a dichotomized three gene DNA methylation signature which also predicts time to PSA recurrence in multivariate analysis significantly in two cohorts.

17:10 Single-Cell Genomics to Study Dna-mutation, Genetic Heterogeneity and DiseaseThierry Voet, Ph.D., Head, Laboratory of Reproductive Genomics, KU Leuven, Belgium; Associate Faculty Member, Wellcome Trust Sanger InstituteWe have developed various wet-lab and computational methods that allow analyzing a solitary cell. We apply these genome-wide methods to study DNA-mutation, genetic heterogeneity and cancer. Furthermore, we developed novel generic single-cell methods for preimplantation genetic diagnosis (PGD) of human cleavage stage embryos in the clinic.

17:35 Close of Symposium

16:00-18:00 main Conference registration

3 December 2013

5

Pre-Conference Symposium: Quantitative Digital Detection technologies08:30 registration and morning Coffee

DIGITAL PCR TECHNOLOGIES AND TECHNIQUES


09:10 Clinical Implementation of ddPCr in the Diagnosis, and management of myeloproliferative neoplasms (mPns)Christopher Campbell, West Midlands Regional Genetics Laboratory, Birmingham Women’s Hospital, United Kingdom

09:40 Value assignment of Certified reference material by dPCr technologiesPhilippe Corbisier, Ph.D., Scientific and Technical Project Manager, Standards for Innovation and Sustainable Development, European Commission - JRC - IRMM, BelgiumdPCR technologies allow us to quantify nucleic acids without the use of standard curve and are therefore particularly suited to characterize nucleic acids standards used as calibrants in quantitative PCR experiments. A number of parameters that affect the accuracy of the measurements will be discussed and results using commercially available microfluidic chamber based PCR and droplet digital PCR will be discussed.

10:10 Global Detection of Braf V600 mutations Using a Wild-type negative Lna Probe-Based Droplet Digital PCr assayCurtis Hughesman, Ph.D., Post-Doctoral Research Fellow, Michael Smith Laboratories, University of British Columbia, CanadaHere we report a reliable method to collectively detect all known BRAF V600 mutations in a single assay using two LNA probes applied in a droplet digital PCR format. We have used this assay to successful screen cell lines and plasmids bearing 8 unique nucleotide mutations at codon 600 of BRAF with an analytical specificity of <0.05%.

10:40 Coffee Break

11:10 Plasma Dna Digital PCr as a noninvasive tool for Detection of Genomic alterations in metastatic Breast CancerGaia Schiavon, M.D., Ph.D., Cridlan Fellow in Medical Oncology – Breast Unit, The Royal Marsden NHS Foundation Trust, United KingdomProof of the concept exists that circulating cell-free DNA (cfDNA) carrying tumor-specific alterations is detectable in plasma of these patients and represents a sensitive biomarker of tumor burden. Performing analysis of cfDNA with digital PCR, we screened for the acquisition of HER2 amplification in metastatic breast cancers and this approach could potentially be adapted to the analysis of any locus amplified in cancer.

11:40 the Use of dPCr to measure Her-2 in Borderline-amplified Breast Cancer research SamplesGabriele Zoppoli, M.D., Ph.D., Internal Medicine Resident, University of Genova & IRCCS AOU San Martino IST, Italy Here, we describe the use of dPCR in a set of ERBB2 “equivocal status” BC patients. We also assess TOP2A copy number, and both TOP2A and ERBB2 gene expression intensity, on the described sample set. We discuss dPCR results compared to those obtained by qRT-PCR, IHC, and aCGH methods.



13:10 Session Break

IMPROVEMENTS TO TRADITIONAL PCR AND MICROFLUIDICS

14:00 Chairperson’s opening remarksN. Reginald Beer, Ph.D., Medical Diagnostics Initiative Leader, Center for Micro and Nanotechnologies, Lawrence Livermore National Laboratory, United States

14:05 Preparative microarrays & Laser Induced Dehybridization: the Intersection of microarrays, PCr, and SequencingN. Reginald Beer, Ph.D., Medical Diagnostics Initiative Leader, Center for Micro and Nanotechnologies, Lawrence Livermore National Laboratory, United StatesThis talk will describe a novel approach using a focused IR laser to dehybridize bound oligos from individual microarray spots. The bound oligos can be 200 bp or longer, providing much more information than just the bases complementary to the short probe sequences. This method has the potential to improve detection and downstream analysis for rare or highly divergent targets in genotyping or microbial discovery applications.

14:35 a novel Platform for Digital Isothermal nucleic acid amplifications Using BartGuy Kiddle, Ph.D., Senior Molecular Biologist, IVD Technologies, Lumora Ltd., United KingdomLumora Ltd. has demonstrated that BART technology (a bioluminescent reporter system for isothermal amplification) in conjunction with loop mediated isothermal amplification (LAMP) represent a novel, highly scalable and low-cost platform for digital amplifications based on CCD camera image capture. The LAMP-BART platform has been demonstrated on two applied challenges. This presentation will highlight the potential of dBART, as a commercial alternative to conventional digital PCR.


15:35 refreshment Break

SINGLE-CELL ANALYSIS METHODS

16:10 Cell Heterogeneity and Single Cell analysis: a new Paradigm for translational medicineFerdinando Mannello, Ph.D., Assistant Professor, Cell Biology, Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cell Biology, University “Carlo Bo” of Urbino, ItalyCellular heterogeneity forms the fundamental principle of cell biology, but the new generation technology of single-cell analysis is able to better characterize cells population, identifying and differentiating outlier cells, and driving beyond the capability of conventional technology. Single-cell analysis is the new frontier in “OMICS”-era, which will become a diffuse and efficient investigational strategy for translational medicine.

16:35 Quantitative High-resolution Genomic analysis of Single Cancer CellsBurkhard Brandt, Ph.D., Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, GermanyWe present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyzes by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centered by the therapeutically relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics.

17:10 Single-Cell Genomics to Study Dna-mutation, Genetic Heterogeneity and DiseaseThierry Voet, Ph.D., Head, Laboratory of Reproductive Genomics, KU Leuven, Belgium; Associate Faculty Member, Wellcome Trust Sanger InstituteWe have developed various wet-lab and computational methods that allow analyzing a solitary cell. We apply these genome-wide methods to study DNA-mutation, genetic heterogeneity and cancer. Furthermore, we developed novel generic single-cell methods for preimplantation genetic diagnosis (PGD) of human cleavage stage embryos in the clinic.

17:35 Close of Symposium

16:00-18:00 main Conference registration

3 December 2013

6

WeDneSDay, 4 DeCemBer

07:30 registration and morning Coffee

TARGETED SEQUENCING

08:30 Chairperson’s opening remarksHans-Hilger Ropers, M. D., Ph.D., Board Certified Clinical Geneticist, Professor of Human Genetics, Humboldt University and Director, Max Planck Institute for Molecular Genetics, Berlin, Germany

» Keynote PreSentatIon08:40 new Sequencing techniques: Why they are Indispensable for Health Care, and What We Can Do to Speed Up their Clinical ImplementationHans-Hilger Ropers, M. D., Ph.D., Board Certified Clinical Geneticist, Professor of Human Genetics, Humboldt University and Director, Max Planck Institute for Molecular Genetics, Berlin, GermanyWhile there is no doubt that the new sequencing techniques will revolutionize genetic diagnosis and health care, their clinical implementation still lags behind. Major reasons for this delay are i. public unawareness of the opportunities of genome sequencing; ii. misconceptions about its dangers, which are related to the failed ‘common disease-common variant’ paradigm; iii. budgetary concerns and in many countries, iv. suboptimal organization of genetic health care which requires a minimum of centralization. However, none of these obstacles are unsurmountable.

09:10 external Quality assessment for nGSDavid E. Barton, Ph.D., Chief Scientist, National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Ireland, United KingdomThe European Molecular Genetics Quality Network (EMQN) provides external quality assessment to genetic testing laboratories world-wide. Experience shows that the introduction of new technologies into clinical diagnostics carries risks. Thorough validation and quality assessment are essential. EMQN, in collaboration with UK NEQAS, ran a pilot EQA for Next-Gen DNA sequencing in 2013. Results of this pilot study will be reported.

09:40 targeted next-Generation Sequencing Can replace Sanger Sequencing in Clinical DiagnosticsJan D. H. Jongbloed, Ph.D., Department of Genetics, University of Groningen, University Medical Centre Groningen, The NetherlandsThis talk will include results of the manuscript on targeted NGS such as recent results of the use of our method in routine clinical diagnostics; a comparison of results in these patients obtained with both targeted and exome sequencing (we have quite some patients that were analyzed with both methods); a study concerning the effect of over dispersion in both methods.

10:10 Coffee Break in the exhibit Hall with Poster Viewing

COMPARING EXOME AND WHOLE GENOME SEQUENCING

10:45 Comparing exome vs. Genome Sequencing for Genetic Component of DiseasesHan G. Brunner, Ph.D., Medical Geneticist, Radboud University Nijmegen Medical Centre, The NetherlandsGiven that a considerable proportion of rare diseases are based in genetics, patients with complex clinical presentation may soon be included in a program for undiagnosed diseases where the first step is exome sequencing. Such a strategy would provide many accurate diagnoses, thereby reducing doctor’s delay, unnecessary invasive, costly and burdensome procedures.

11:15 Comparing Clinical v. Whole exome Sequencing for monogenic Diseases and Undiagnosed PatientsPascal Joset, Ph.D., Research Associate, Institute of Medical Genetics, University of Zurich, SwitzerlandThe advent of NGS techniques is paving the way for novel large scale approaches with an unforeseen diagnostic power. While whole exome sequencing may provide theoretically the highest cost-efficient power, it may miss mutations due to incomplete coverage. We therefore evaluated the power of a “clinical exome” limited to about 2700 genes with currently known monogenic mutations.



13:15 Session Break

14:00 Chairperson’s remarksGholson J. Lyon, M.D., Ph.D., Assistant Professor of Human Genetics, Cold Spring Harbor Laboratory and Research Scientist, Utah Foundation for Biomedical Research, United States

14:05 Increasing accuracy for exome and Whole Genome SequencingGholson J. Lyon, M.D., Ph.D., Assistant Professor of Human Genetics, Cold Spring Harbor Laboratory and Research Scientist, Utah Foundation for Biomedical Research, United StatesOur recent results suggest that more caution should be exercised in genomic medicine settings when analyzing individual exomes and genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.

14:35 Changing the Clinical Genetic testing Paradigm: reducing Cost and Increasing UtilitySteve Lincoln, Senior Vice President, Scientific Applications, InVitae, United States

15:05 experiences from our Integrated Genomics Clinic; rapid Identification and Clinical reporting of Causative mutations through WGS and WeSElizabeth Worthey, Ph.D., Human and Molecular Genetics Center, The Medical College of Wisconsin, United StatesMCW’s Genomic Medicine Clinic has been operational for more than 18 months. As the first genomics based integrated genetics clinic of its kind its development required definition of appropriate: patient counseling, analysis, interpretation, and reporting. I will discuss how to incorporate genomic data to support diagnosis with a particular focus on the informatics as well as providing discussion of the discoveries, challenges and lessons learned applying NGS in the clinic.


16:05 refreshment Break in the exhibit Hall with Poster Viewing

16:45 exome Sequencing in Complex Disease: Data Quality and Clinical HeterogeneitySarah Ennis, Ph.D., Associate Professor, Head, Genomic Informatics, Genomic Informatics, University of Southampton Human Genetics & Genomic Medicine, United KingdomThis talk will present key aspects in the exome analysis of a cohort of paediatric patients diagnosed with severe inflammatory bowel disease. The talk will outline some key issues with regard to data management and quality and go on to present approaches to pathway analysis in complex disease and present key findings that underpin disease in individual patients.

17:15 Panel Discussion with Day’s Speakers

17:45 Welcome reception in the exhibit Hall with Poster Viewing

19:15 Close of Day

tHUrSDay, 5 DeCemBer

08:00 morning Coffee

DEVELOPING TECHNOLOGIES AND INTERFACE FOR INTERPRETING GENOMES

08:30 Chairperson’s opening remarksGerman Pihan, M.D., Staff Pathologist and Director, Hematopathology Service, Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, United States

Clinical exome SequencingInaugural

Sequencing4-5 December 2013

Changing the Nature of Genetic Diagnosis

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08:35 Strategies for Disease-Gene Identification in exome SequencingPeter N. Robinson, Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, GermanyWhole exome sequencing (WES) is revolutionizing many areas of diagnostics and research in human genetics, but the sheer number of candidate genes revealed by typical WES studies represents a challenge to medical and biological interpretation. We will present new algorithms for utilizing phenotypic analysis and protein interaction networks to effectively prioritize candidates in exome sequencing studies.

09:05 the Post-WGS Cancer Genome: alphabet Soup, Syllabus or Cyclopaedia?German Pihan, M.D., Staff Pathologist and Director, Hematopathology Service, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, United StatesReview of how the WGS cancer genome data deluge is changing our views of the pathogenesis and biology of cancer as well as how the new knowledge may be harnessed to combat the “Emperor of all maladies.”



10:45 Integrated exome Sequencing and Copy number analysis of Pancreatic Cancer reveals a Her2-amplified SubtypeMark Cowley, Ph.D., Senior Bioinformatics Research Officer, Genome Informatics & Clinical Genomics, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, New ZealandWe have recently performed WES and copy number analysis from 99 pancreatic ductal adenocarcinoma tumors within the ICGC. By copy number analysis, and supported by WGS, microarray analysis, IHC and FISH, we identified a case with HER2-amplification. Our results have potentially defined the first targeted therapy for pancreatic cancer, which we are taking to an adaptive clinical trial.

11:15 Bringing the Big Brain Computer to the Cloud: Sponsored by SGI UV for Cloud-Based Genomics WorkflowsJames Reaney, Senior Director, Research Markets, SGIBuilding on years of experience with Cyclone™, SGI announces a new collaborative project to bring cloud-based computational resources to genomics workflows worldwide. SGI will showcase several of its computational and storage technologies in the project but chief among these is the SGI UV platform: the “Big Brain” supercomputing system which already powers several large genomics research facilities worldwide. A very brief, high-level overview of the project and it’s collaborative approach will be given, along with a discussion of the initial goals.

» PLenary Keynote11:45 from Genome annotation to Genome medicineTimothy Hubbard, Ph.D., Senior Group Leader, Wellcome Trust Sanger Institute, United KingdomI will describe the status of the human genome sequence and its annotation, in particular the generation of the GENCODE geneset as part of the ENCODE project and the impact of RNA-seq. I’ll also discuss the latest human genome assembly from the Genome Reference Consortium (GRC). As the UK plans to sequence 100,000 human genomes in the National Health Service (NHS), I’ll discuss requirements for integrating genomics into healthcare systems and summarize progress towards genomic medicine in UK.

12:35 Close of Conference

Clinical exome SequencingInaugural


Changing the Nature of Genetic Diagnosis

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11:30 Conference registration


12:35 enjoy Lunch on your own

ADVANCES IN RNA-SEQ DATA ANALYSIS


14:05 De Novo full-Length transcriptome analysis by a Hybrid Sequencing approach Wei Chen, Ph.D., Senior Scientist & Group Leader, Max Delbruck Center for Molecular Medicine, GermanyI will present a hybrid sequencing approach based transcriptome analysis pipeline that reports high quality transcripts in their full length independent of reference genome sequences. Using full-length cDNA libraries in conjunction with Single Molecule Read-Time (SMRT) DNA sequencing technology, we can directly capture the full-length transcripts, but with low sequencing accuracy. To report high quality transcriptome, we then developed a novel computational tool, IPEC, which utilizes the high quality Illumina sequencing data to correct random errors generated.

14:35 Detecting Differential Splicing employing Splicing Compass on rna Sequencing DataRainer König, Ph.D., Group Head, Divisions of Theoretical Bioinformatics, Heidelberg University, GermanyThe emergence of next-generation RNA sequencing (RNA-seq) provides an exciting new technology to analyze alternative splicing on a large scale. We present a new method and software to predict genes that are differentially spliced between two different conditions using RNA-seq data. Our method employs geometric angles between the high dimensional vectors of exon read counts. With this, differential splicing can be detected even if the splicing events comprise of higher complexity and involve previously unknown splicing patterns.

15:05 a Hybrid approach to Comprehensive transcriptome reconstruction Using Genome-Guided and de novo rna-Seq assembly Leveraging trinity and PaSa2Brian Haas, Manager, Genome Annotation, Outreach, Bioinformatics and Analysis, The Broad Institute, United StatesExisting reference genomes or draft genome assemblies may yield a limited view of the transcript content of a sample due genome misassembly, sequencing gaps, or genuine sequence variation between sequenced samples and available reference genomes. Here we present a hybrid approach that combines genome-guided and de novo RNA-Seq assembly to annotate gene structures and capture those transcripts missing or otherwise insufficiently represented by genome assemblies. We demonstrate our approach to be highly effective across diverse eukaryotes and to the restructured genomes of human breast cancer cell lines.

15:35 Interpreting Genomic Variation in the research Sponsored by and Clinical Context Using omicsoffice on the Spotfire analytics PlatformEduardo Gonzalez-Couto, Ph.D., CSO, Integromics, SpainGenomic variants studies require a subtle combination of enrichment, with diverse biological and clinical annotations, followed by filtering and ranking of the annotated variants. The OmicsOffice intelligence suite clinical workflow is designed to enable researchers and clinicians to easily explore variants, pinpoint known facts as well as discover novel associations.



DISEASE INTERROGATION & CLINICAL APPLICATIONS OF RNA-SEQ

17:20 alternative Protein-Coding transcripts in Prostate CancerMelanie Lehman, Ph.D., Research Fellow, Australian Prostate Cancer Research Centre, Queensland University of Technology, AustraliaWe have applied de novo transcriptome assembly methods to RNA-seq data to profile RNA expression in prostate cancer cells. We have identified alternative protein-coding RNAs that are missing canonical functional domains as well as long coding RNAs (lncRNAs) that are overlapping—and often mistaken for—protein-coding RNAs. We will present the implications of these alternative transcripts to pathway and functional analysis in the context of our research in late stage prostate cancer.

17:50 Deciphering the neuroblastoma transcriptome by rna-Seq, qPCr and exon-Level resolution array analyzesAlexander Schramm, Ph.D., Lab Head, Oncology Research, Children’s Hospital, University Hospital Essen, GermanyDuring my presentation, I will report on integration of technologies required to understand which coding and non-coding RNAs are transcribed in a cancer cell. Results from array-based technologies, qPCR and next-generation RNA-seq will be compared using the embryonal tumor, neuroblastoma, as a model system. An automated workflow for the analyses of RNA-seq data will be presented. Finally, I will discuss some ideas for integrating NGS data into clinical decision making.

18:35 Close of Day

frIDay, 6 DeCemBer


DISEASE INTERROGATION & CLINICAL APPLICATIONS OF RNA-SEQ (CONT.)


08:35 Lighting Up the Dark matter: targeted rna Sequencing reveals novel non-coding rnas transcribed from Intergenic Disease-associated regionsMarcel Dinger, Ph.D., Head, Clinical Genomics, Garvan Institute of Medical Research, AustraliaThe relatively recent discovery of widespread transcription of potentially functional long noncoding RNAs (lncRNAs) from the mammalian genome led us to investigate whether or not GWAS hits in noncoding regions could be reconciled by the transcription of regulatory RNAs from these loci. To detect such specifically expressed transcripts, we used capture arrays targeting 350 noncoding regions of the genome associated with disease and sequenced the captured RNA transcribed from these regions. We have identified >1,500 new lncRNAs whose expression appears to be specifically associated with disease.

09:05 Using rna-Seq to Identify and Characterize Cancer-Specific transcript VariantsRolf I. Skotheim, Ph.D., Group Leader, Genome Biology, Department of Cancer Prevention, Oslo University Hospital, NorwayThe presentation will include recent results where novel fusion genes are identified from colorectal cancer cell lines by combined paired-end RNA sequencing and whole-genome sequencing, and demonstrated to be commonly expressed in clinical cancer specimen. Furthermore, cancer specific promoter usage have led to the expression of a transcript variant not previously described, and the talk will cover description on how this was identified and characterized as specifically expressed in colorectal cancer. Further, in analogy with various genomic instabilities, transcriptome instability will be described as a novel phenotype to cancers of several different origins.

09:35 Using nGS and in vitro models to Understand Structural and regulatory Variation in Gastric CancerCarla Oliveira, Ph.D., Head, Expression Regulation, Cancer Group, IPATIMUP, PortugalGastric carcinoma (GC) is the second leading cause of cancer death worldwide with

rna-Seq and transcriptome analysisInaugural


Unraveling Layers of Expression

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over 700,000 deaths per year. A systematic approach to identify subgroups of gastric cancer based on clinico-pathologic features, cancer-specific molecular profiles and patients’ survival is missing. We followed a strategy of gastric cancer stratification based on rigorous histo-pathology characterization and molecular profiling according to three important prognostic factors in gastric cancer (E-cadherin LOH, MSI and HER2). A collaborative team from IPATIMUP, Coimbra Genomics and BGI is currently performing WGRS, RRBS and RNA-seq of 50 pairs of stratified gastric cancers and paired normal tissue. Adequate bioinformatics pipelines and in vitro models, to validate candidate pathways emerging from our NGS approach, are in place at IPATIMUP. We hope to shed light onto GC-specific molecular signatures crucial for the identification of therapy targets and for the development of new therapeutic options.


EXPLORING THE COMPLEXITY OF THE TRANSCRIPTOME

10:45 the Identification of Long Stress-Induced non-Coding transcriptsDavid I. Smith, Ph.D., Professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, United StatesIn an attempt to identify important regulatory transcripts we previously utilized whole genome tiling arrays to examine the entire genomes response to the cellular stress of the tobacco carcinogen NNK. This enabled us to identify 12 long non-coding transcripts which we have termed LSINCTs (for long-non-coding stress induced transcripts). I will describe some of the work that we have done to characterize these interesting transcripts. A much better way to identify such transcripts is the use of RNA-seq and we have since used this to characterize the transcriptional changes that occur during the development of head and neck cancer. A number of transcripts identified from the RNA-seq head and neck data correspond to the LSINCTs that were identified from the original tiling array experiment.

11:15 Profiling micrornas and Circular rnas in Brain – Implication for Disease and DevelopmentJørgen Kjems, Ph.D., Professor & Director, Department of Molecular Biology and Genetics, Aarhus University, DenmarkCircular RNA (circRNA) has recently been established as significant regulator of miRNA activity and evidence suggest that differential expression of circRNA may play a role in tissue development end progression of disease. In particular microRNA-7 appears to be tightly controlled by a circular RNA sponge for miR-7 (ciRS-7) in a dynamic fashion in brains from placental animals. The resemblance of pig brain to humans makes it an interesting model to study the role of miRNA in development. We have profiled mRNA, miRNA and ciRS expression in fetal pig brains and uncovered novel non-coding RNA controlled pathways involved in brain development.

11:45 regulation of transcriptional Heterogeneity by Chromatin and transcription machineryVicente Jose Pelechano, Ph.D., Senior Scientist, Steinmetz Group, Genome Biology, EMBL, GermanyBy jointly determining both transcript ends for millions of RNA molecules (TIF-Seq), we have recently revealed an extensive layer of isoform diversity previously hidden among overlapping RNA molecules. Given the existence of overlapping, variable transcript isoforms, determining the functional impact of the transcriptome requires identification of full-length transcripts, rather than just the genomic regions that are transcribed. Here, by systematically applying TIF-Seq to yeast mutants involved in transcription regulation and chromatin organization, we will present new insights in how this extensive transcript diversity can be generated by a relatively simple eukaryotic genome with limited splicing, and within a genetically homogeneous population of cells. We will specially focus on the implications of this diversity for increasing protein diversity and the expression of alternative isoforms that vary in post-transcriptional regulatory elements.

>> Keynote PreSentatIon

12:15 the ethical Dimensions of Data Sharing and the maze of IdentifiabilityAnne Cambon-Thomsen, M.D., Director, Research, Centre National de la Recherche Scientifique (CNRS), FranceThe policies of data sharing are strongly re-affirmed by numerous research institutions and funders. This movement in the context of the availability of large-scale sequencing technologies for studying human genomic variation is confronted with the legal and ethical aspects regarding privacy, confidentiality, clinically useful information and the duties attached. Issues related to identifiability, consent process and regulation of access especially challenge the existing framework. Current developments will be discussed.


13:15 Session Break

REFINING EXPRESSION ANALYSIS

14:00 Chairperson’s opening remarksMary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Insitute (CHI), United States

14:05 Standards in rna-Seq Data analysisStuart Brown, Ph.D., Associate Professor, Cell Biology; Director, Sequencing Informatics Group of Center for Health Informatics & Bioinformatics, NYU School of Medicine, United States

14:35 rna-Seq and microarray Gene expression Vie for Superiority within a Comprehensive Study DesignWeida Tong, Ph.D., Division Director, Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, FDA, United StatesThe 3rd phase of the FDA-led community wide Microarray Quality Control (MAQC-III) project investigated the reliability and utility of RNA-Seq. All the samples in this project were profiled by both RNA-Seq and microarrays, which produced unprecedented opportunity to comprehensively compare RNA-seq with microarrays. RNA-Seq seems to provide comparable or better transcriptomic profiling as compared with the standard microarray technology for the elucidation of biological responses. This project involves ~200 participants from >80 organizations with comprehensive results that will impact FDA policy.

15:05 multi-Platform and Cross-methodological reproducibility of transcriptome Profiling by rna-Seq in the aBrf next-Generation Sequencing Study (aBrf-nGS)Christopher Mason, Ph.D., Assistant Professor, Computational Biomedicine, Weill Cornell Medical College, United StatesWe use standard reference samples to evaluate RNA-Seq across a range of sample quality levels, sample preparation methods and bioinformatics analysis approaches, with results that have the potential to improve the utility and comparability of these various methods and five NGS platforms (Illumina, PacBio, 454, PGM, Proton). Importantly, we demonstrate that even severely degraded RNA, when prepared and analyzed with appropriate methods, can be as useful as intact RNA for sequencing-based quantitative profiling.

15:35 functional Dysregulation in Inflammatory Diseases Carsten O. Daub, Ph.D., Assistant Professor, Biosciences and Nutrition & Science for Life Laboratory, Karolinska Institutet, SwedenEmploying genome-wide expression profiling for contrasting disease and control patients allows not only identification of differentially regulated protein or non-coding transcripts but also inference of the underlying regulatory events.


Inaugural


rna-Seq and transcriptome analysis Unraveling Layers of Expression

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4-5 December 2013 Informatics

High-Scale Computing Turning Big Genomics Data into Smart DataFifth Annual

WeDneSDay, 4 DeCemBer

07:30 registration and morning Coffee

SUPPORTING GENOMICS WITH IT INFRASTRUCTURE08:30 Chairperson’s opening remarksJanis E. Landry-Lane, Program Director, World Wide High Performance Technical Computing, Life Sciences/Higher Education Segments, IBM

» Keynote PreSentatIon08:40 eLIXIr: the european research Infrastructure for Life Science DataNiklas Blomberg, Ph.D., ELIXIR Director, ELIXIR Hub, EMBL-EBI, United KingdomThe mission of ELIXIR is to construct and operate a sustainable infrastructure for the sharing of biological information throughout Europe, to support life science research and drive its translation to medicine and the environment, the bio industries and society. The challenges in storing, integrating and analyzing the data from modern biological experiments are real; ELIXIR meets this challenge through a distributed e-infrastructure of bioinformatics services built around established European centres of excellence.

09:10 Scalability, reproducibility and traceability in Large-Scale nGS facilitiesGianmauro Cuccuru, Ph.D., Researcher, CRS4 Bioinformatics Laboratory, ItalyAs the rate of samples to process increases, manually performing and tracking operations becomes increasingly difficult, costly and error-prone, while processing the massive amounts of data poses significant computational challenges. We will present how combining scientific workflow applications (Galaxy) with state-of-the-art processing technologies like Hadoop, OMERO and iRODS can help address these challenges, thus, empowering more complex life science studies while providing scalability, full reproducibility and traceability.

09:40 Providing the Clinical Genomics Platform: a How-to Guide for flexible and extensible Services for Clinical Big DataBrent Richter, Executive Director, Enterprise Research Infrastructure & Services, Information Systems & Academic Programs, Partners HealthCare & Massachusetts General Hospital/Brigham & Women’s Hospital, United StatesManaging NGS data and reporting results require secure but extensible infrastructures. Continuing to adopt these platforms to additional clinical areas such as pathology and microbiotics is the current challenge, but the future brings the promise of network medicine that incorporates all information about a patient, from genomics to real-time imaging. What will be the information technology architectures required that places storage, networks and analytics together in a secure and available environment? What services need to be developed?


10:45 1000 Genomes/UK10K Projects: Data management and Data SharingThomas Keane, Ph.D., Senior Scientific Manager, Vertebrate Resequencing Informatics, Wellcome Trust Sanger Institute, United KingdomWe have now reached the point where large-scale human disease association studies are carried out primarily using next-generation sequencing technologies. These studies can generate many hundreds of terabases of sequencing data. One of the key challenges is to devise scalable and robust data management and data sharing solutions. In this talk, I will cover how we have addressed these challenges at the Wellcome Trust Sanger Institute.

11:15 Implementation of translational Informatics in the ClinicJesper Tegnér, Ph.D., M.D., Professor, Strategic Chair, Computational Medicine and Director, Unit of Computational Medicine, Center for Molecular Medicine, Medicine, Karolinska Institutet and Karolinska University Hospital, SwedenThere is an urgent need to manage and integrate different data types originating from molecular translational research and healthcare. In collaboration with clinicians, we have implemented a system integrating 15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per patient and clinical database with 5652 clinical visits for a cohort of 379 patients. Basic functionalities include research data management, development of bioinformatics workflow and analysis, sub-cohort selection and reuse of clinical data in research settings. We will describe the challenges and solutions inherent in this kind of work.

11:45 an Integrated High Performance Computing PlatformSponsored by

for Genomics and translational researchJanis E. Landry-Lane, Program Director, World Wide High Performance Technical Computing, Life Sciences/Higher Education Segments, IBM

Tzy-Hwa (Kathy) Tzeng, Ph.D., Senior Technical Staff Member, IBM Life Science and NGS SolutionHigh-performance computing and storage are required to efficiently process data generated by NGS. The applications used to map reads and detect variants are typically CPU and I/O intensive. IBM has characterized this workload and developed optimal genomics platform to address the demand. The goal of any sequencing project is to gain insight into diverse range of biological processes by integrating genome data with corresponding phenotypes. Large computational capacity and sophisticate algorithms are mandatory in the translational platform. We will illustrate how IBM seamlessly integrates genomics and translational platforms.


13:15 Session Break

CLOUD AS A COMPUTING RESOURCE

14:00 Chairperson’s opening remarksPer Hansen, Technical Specialist EMEA, Aspera, Inc.

14:05 Cloud4Science: Using Public Clouds in nGS PipelinesIgnacio Blanquer, Ph.D., Associate Professor/Researcher, Computer Systems/Institute of Instrumentation for Molecular Imaging, Universitat Politècnica de València, SpainCloud4Science is an initiative funded by Microsoft to boost the use of clouds in science. The first prototype focuses on genomics on the cloud (www.cloud4science.eu) and integrates a complete pipeline for mutation detection analysis running on Windows Azure cloud, which users can easily deploy and run using their Azure credentials. Cloud4Science has focused on the issues in data transfer, provenance and massive processing from a user-friendly portal that transparently deploys the needed resources.

14:35 Cost-effective GPU-Grid for Genome-Wide epistasis CalculationsBenno Pütz, Ph.D., Statistical Genetics, Max Planck Institute of Psychiatry, GermanyWith local restrictions on handing out clinical data to external computer centers, the cloud, we were forced to establish appropriate computing resources in-house as an alternative solution. From a price/performance point of view, low-cost systems based on consumer graphics cards turned out to be our best option. The system setup as well as some of the work performed on epistasis will be presented.

15:05 CloudmC: a Cloud Computing Platform for radiation CalculationsHector Miras, Medical Physicist, Department of Medical Physics, Virgen Macarena University Hospital, Spain

Rubén Jiménez, Chief Software Architect, R&D Division, Icinetic, SpainMonte Carlo (MC) algorithms are considered the gold standard for radiation calculations, but they are computationally expensive. That is why they are not used in routine clinical practice. CloudMC is a platform developed on Windows Azure intended for parallelization of radiation calculations using MC algorithms. This platform allows any user to have access to a big computing power to perform MC simulations paying only for the resources used.

15:35 High-Speed Data movement for Global Sponsored by Collaboration in Genomic research - Bridging enterprise and Cloud Infrastructure for effective Global Collaboration in Life SciencesMichelle Munson, Founder & CEO, Aspera, Inc.


16:45 Bioinformatics Use Cases for Cloud ComputingMohamed M. El-Kalioby, Research Scientist, Bioinformatics Group, Center for Informatics Science, Nile University, EgyptBioinformatics data is getting larger and larger every day, especially after NGS. Computation infrastructure required to handle this is getting harder and is expensive to build. How can we utilize the scalability and availability of cloud computing for such activities?


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17:15 the eUDat Project and Cloud StorageWolfgang Gentzsch, Ph.D., Co-Founder, The UberCloud HPC Experiment; Executive Consultant, HPC, Grid and Cloud; Advisor, EUDAT; Chairman, ISC Cloud Conferences, GermanyEUDAT aims to develop and support a Collaborative Data Infrastructure allowing researchers to share data across communities and carry out research effectively. EUDAT’s data services, like persistent storage, identification, authenticity, workflow execution and mining, can leverage cloud storage. But copyright or national law might not allow the data to leave the country or even the data centre in which they are curated. EUDAT takes a long-term view of the data it holds and is considering “trust marks” for digital archiving.

17:45 Welcome reception in the exhibit Hall with Poster Viewing

19:15 Close of Day



NGS DATA MANAGEMENT AND ANALYTICS

08:30 Chairperson’s opening remarksMaria Burpee, Marketing Manager, EMEA Healthcare, Dell

08:35 Preprocessing of High-throughput Sequencing Data Speeds Up targeted researchTomasz Konopka, Ph.D., Research Scientist, Sebastian Nijman Laboratory, Informatics and Synthetic Biology, CeMM, Research Center for Molecular Medicine, Austrian Academy of Sciences, AustriaInformation encoded in high-throughput sequencing reads can be valuable for targeted hypothesis-driven research questions. It is thus worthwhile to access relevant portions of large datasets in fastq format without costly processing of the remainder. The TriageTools suite available on SourceForge provides fast utilities for preprocessing fastq data. It includes a method for extracting reads likely to map onto predefined regions of interest and extracting data on a few DNA- or RNA-seq samples’ target genes with speedup factors up to ~90.

09:05 Compression models for Dna SequencesArmando J. Pinho, Ph.D., Director, Instituto de Engenharia Electrónica e Telemática de Aveiro (IEETA) and Associate Professor, Departamento de Electrónica, Telecomunicações e Informática (DETI), Universidade de Aveiro, PortugalResearch in the genomic sciences is confronted with the volume of sequencing and resequencing data increasing at a higher pace than that of data storage and communication resources, shifting a significant part of research budgets from the sequencing component of a project to the computational one. Hence, being able to efficiently store sequencing and resequencing data is a problem of paramount importance. In this talk, we will present and discuss DNA sequence compression models that we have been developing during the past years.

09:35 HPC for Life Sciences: accelerate Discovery Sponsored by and Insights through optimized Infrastructure and SupportKris Buggenhout, HPC Solutions Architect, Dell EMEAProliferation of low-cost, efficient Next Generation DNA Sequencing (NGS) systems is accelerating the creation of large scale databases, driving increasing demand for compute and storage resources to aggressively analyze their content. This presentation will outline how a high performance computing environment can be optimized for the needs of genomic analysis, enabling organizations to accelerate time-to-insight with easy-to-deploy, open standards-based architectures designed for performance, scalability and efficiency.


10:45 management of Genomic Big Data in a Country-Wide Collaborative Initiative for rare Disease Gene findingJoaquin Dopazo, Ph.D., Head, Computational Genomics, Centro de Investigacion Principe Felipe, SpainAbout 1000 exomes were analyzed in a nationwide initiative to find disease genes in many inherited diseases. This flood of DNA and RNA-seq data led to pipeline optimization for NGS data analysis, including accelerating runtimes and increasing sensitivity in mapping and variant calling processes, the development of new visualization tools and the development of new systems-biology-based candidate gene prioritization methods. The Medical Genome Project and the Spanish network for Rare Diseases constitute an example of a collaborative nationwide genome project.

11:15 Bringing the Big Brain Computer to the Cloud: Sponsored by SGI UV for Cloud-Based Genomics WorkflowsJames Reaney, Senior Director, Research Markets, SGIBuilding on years of experience with Cyclone™, SGI announces a new collaborative project to bring cloud-based computational resources to genomics workflows worldwide. SGI will showcase several of its computational and storage technologies in the project but chief among these is the SGI UV platform: the “Big Brain” supercomputing system which already powers several large genomics research facilities worldwide. A very brief, high-level overview of the project and it’s collaborative approach will be given, along with a discussion of the initial goals.




High-Scale Computing Turning Big Genomics Data into Smart DataFifth Annual


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11:30 Conference registration


12:35 enjoy Lunch on your own

ANALYTICAL TOOLS

14:00 Chairperson’s opening remarksSimone Sharma, Regional Marketing Specialist, Data Analytics, Perkin Elmer Informatics

14:05 annotate-it and eXtasy: Interpretation and Prioritization of Single-nucleotide Variation in Clinical GenomicsAlejandro Sifrim, Ph.D., Research Scientist, Yves Moreau Laboratory, Bioinformatics, Electrical Engineering, Katholieke Universiteit Leuven, BelgiumThe human genome harbors a plethora of neutral, common and rare variations. In order to find the cause of genetic disease, one must be able to distinguish these neutral variants from the disease-causing variants. Here we present Annotate-it and eXtasy, two software tools which aid the clinical geneticist in discovering disease-causing SNVs.

14:35 taG (tumor analysis in Galaxy): a Web Server application for the Detection of Somatic mutations in the absence of associated Healthy ControlAndrew Stubbs, Ph.D., Assistant Professor, Bioinformatics, Erasmus University Medical Center, The NetherlandsThe first step in tumor analysis is typically a correction with a normal sample, taken from the individual’s healthy tissue for which 80%-95% of variations in a tumor sample present in the healthy tissue. We have developed a web-based, control-free tumor analysis and reporting application with a “virtual normal” as reference to determine somatic mutations. It removed up to 97% of the variants detected by the standard tumor/normal approach. We will present our analysis, available in a public Galaxy/CLOUD.

15:05 Harnessing e-Science Central for nGSSimon Woodman, Ph.D., Senior Research Associate, Systems Research Group, School of Computing Science, Newcastle University, United KingdomThe talk will be about how we use e-Science Central for analyzing NGS data within the Cloud4Science project. This will include the pipelines we have implemented and challenges faced by storing and analyzing very large data sets. I will also examine the importance of provenance capture and analysis in this environment.

15:35 Interpreting Genomic Variation in the research Sponsored by and Clinical Context Using omicsoffice on the Spotfire analytics PlatformEduardo Gonzalez-Couto, Ph.D., CSO, Integromics, SpainGenomic variants studies require a subtle combination of enrichment, with diverse biological and clinical annotations, followed by filtering and ranking of the annotated variants. The OmicsOffice intelligence suite clinical workflow is designed to enable researchers and clinicians to easily explore variants, pinpoint known facts as well as discover novel associations.


EXOME SEQUENCING

16:50 Big Science & Biomedicine at Petascale Sponsored by

Andrew McCabe, CTO, EMEA Healthcare, EMCThe exponential decline in the cost of next generation sequencing is making it possible to

discover rare genetic variants that explain uncommon childhood diseases and cancer. To detect these rare variants requires the aggregation and analysis of genomics and clinical data at scale. Consequently the need to manage and to compute biomedical data at scale is driving the dramatic rethinking and re-architecting of IT infrastructures. We will explore best practices for managing data at petabyte scale.

17:20 Sequenza – a Bayesian analytical framework to Provide Comprehensive Characterization of tumor Samples Based on exome SequencingZoltan Szallasi, M.D., Senior Research Scientist, Children’s Hospital Informatics Program, Harvard Medical School, United States and Professor, Systems Biology, Danish Technical University, DenmarkWe are presenting here a powerful bayesian statistics-based analytical framework to analyze exome sequence data from tumor biopsies. Sequenze produces accurate estimates on normal tissue contamination and ploidy levels. It produces highly accurate mutational calls and also enables to extract loss of heterozygosity and copy number variations as accurately as SNP array profiles. We will also present several clinical case studies where Sequenza-based analysis of tumor exome sequences produced valuable clinical information.

17:50 Whole-exome Sequencing in Heterogeneous neurodegenerative DiseasesConceição Bettencourt, Ph.D., Research Associate, Molecular Neuroscience, Institute of Neurology, University College London, United KingdomHereditary spastic paraplegias (HSPs) constitute a group of clinically and genetically heterogeneous neurodegenerative diseases. More than 50 loci and 30 genes have already been identified and, therefore, a gene-by-gene diagnostic approach is becoming unpractical. This talk will focus on the utility of whole-exome sequencing making easier the identification of mutations, and further extending the clinical spectrum of these heterogeneous diseases.

18:20 Close of Day

frIDay, 6 DeCemBer


THERAPEUTIC TARGETS

08:30 Chairperson’s opening remarksAndrew McCabe, CTO, EMEA Healthcare, EMC

08:35 Clinical Genome architecture Circuitry and next-Generation Cancer Drug targetsDimitrios H. Roukos, M.D., Ph.D., Founding Director, Centre for BioSystems & Genomic Network Medicine, CBS.GenNetMed and Department of Surgery, Ioannina University School of Medicine, GreeceThe ENCODE data change the “central dogma” of one-gene/protein-one phenotype which continues to represent the foundation of all drugs developed and currently used in clinical practice. Latest advances in clinical genomics and dynamic signaling networks are presented revealing the exciting perspectives and challenges in targeting individual cancer patient and discovering the next-generation transcriptional circuitry-based drugs. Challenges and perspectives of genomic network medicine are discussed.

09:05 Big Data in Drug Discovery – Challenges and PerspectivesPhilip Groth, Ph.D., IT Business Partner, CoE Research, Bayer HealthCare Pharmaceuticals, GermanyAfter the discovery that mutations influence cancer initiation and development, targeted drugs like Crizotinib or Imatinib have shown dramatic effects on treatment of some cancers. To deepen understanding of the role of mutations in cancer, NGS has been employed to generate large-scale genomic mutation data. These “Big Data” must be stored, processed and analyzed to develop innovative cancer treatments. We present perspectives on cancer sequencing efforts, insights into the manifold technical, ethical, legal and scientific challenges and some solutions.

09:35 Using nGS and in vitro models to Understand Structural and regulatory Variation in Gastric CancerCarla Oliveira, Ph.D., Head, Expression Regulation, Cancer Group, IPATIMUP, PortugalGastric carcinoma (GC) is the second leading cause of cancer death worldwide with over 700,000 deaths per year. A systematic approach to identify subgroups of gastric cancer based on clinico-pathologic features, cancer-specific molecular profiles and patients’ survival is missing. We followed a strategy of gastric cancer stratification based on rigorous histo-pathology characterization and molecular profiling according to three important prognostic factors in gastric cancer (E-cadherin LOH, MSI and HER2). A collaborative team from IPATIMUP, Coimbra Genomics and BGI is currently performing


Genome Informatics Deciphering Disease through Sequencing DataSecond Annual

13

WGRS, RRBS and RNA-seq of 50 pairs of stratified gastric cancers and paired normal tissue. Adequate bioinformatics pipelines and in vitro models, to validate candidate pathways emerging from our NGS approach, are in place at IPATIMUP. We hope to shed light onto GC-specific molecular signatures crucial for the identification of therapy targets and for the development of new therapeutic options.


TRANSLATION INTO THE CLINIC

10:45 the ethical Introduction of Genome-Based Information and technologies into Public HealthHeidi Carmen Howard, Ph.D., Assistant Professor, Biomedical Ethics, IQ Healthcare, Radboud University Medical Centre, Netherlands and Senior Research Fellow, Département d’épidémiologie et de Santé Publique, INSERM, Faculté de Médecine, Université Toulouse, FrancePublic health genomics, wherein genomics would be integrated in all aspects of healthcare and public health, is gradually being proposed as a future reality. And, although laudable, these advances also bring with them a slew of ethical and social issues that challenge the normative frameworks used in clinical genetics until now. With this in mind, we highlight herein five principles that are used as a primer to discuss the ethical and responsible introduction of genome-based information and genome-based technologies into public health.

11:15 Challenges of translation of next-Generation Sequencing to Clinical PracticeÁngel Carracedo, Ph.D., Director, Fundación Galega de Medicine Xenómica (FPGMX), Hospital Clínico Universitario, SpainWe will discuss some of challenges of the use of NGS for the diagnosis of Mendelian diseases and pharmacogenomics. Some of the main problems need advanced bioinformatics tools and are related to the amount of the data generated and the interpretation of variants of uncertain significance. We will show our approaches to face these problems.

11:45 How the electronic Healthcare record Can facilitate Sponsored by

translational and Integrative medicineAmnon Shabo, Ph.D., Project Leader, IBM Healthcare & Life Sciences Standards Program, IBM Haifa Research LabHealth records could include various types of information generated along the translational continuum from discovery to policy and thus could facilitate the translational processes and enable meaningful reasoning by clinical decision support applications. To harmonize the various types of information, it is important to develop a universal health information language that is based on several languages/formats to represent data and knowledge. New effort in Clinical Genomics standardization will be presented.

» Keynote PreSentatIon12:15 the ethical Dimensions of Data Sharing and the maze of IdentifiabilityAnne Cambon-Thomsen, M.D., Director, Research, Centre National de la Recherche Scientifique (CNRS), FranceThe policies of data sharing are strongly re-affirmed by numerous research institutions and funders. This movement in the context of the availability of large-scale sequencing technologies for studying human genomic variation is confronted with the legal and ethical aspects regarding privacy, confidentiality, clinically useful information and the duties attached. Issues related to identifiability, consent process and regulation of access especially challenge the existing framework. Current developments will be discussed.


13:15 Session Break

RNA-SEQ

14:00 Chairperson’s opening remarksMary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Insitute (CHI), United States

14:05 Standards in rna-Seq Data analysisStuart Brown, Ph.D., Associate Professor, Cell Biology; Director, Sequencing Informatics Group of Center for Health Informatics & Bioinformatics, NYU School of Medicine, United States

14:35 rna-Seq and microarray Gene expression Vie for Superiority within a Comprehensive Study DesignWeida Tong, Ph.D., Division Director, Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, FDA, United StatesThe 3rd phase of the FDA-led community-wide Microarray Quality Control (MAQC-III) project investigated the reliability and utility of RNA-Seq. All the samples in this project were profiled by both RNA-Seq and microarrays, which produced unprecedented opportunity to comprehensively compare RNA-seq with microarrays. RNA-Seq seems to provide comparable or better transcriptomic profiling as compared with the standard microarray technology for the elucidation of biological responses. This project involves ~200 participants from >80 organizations with comprehensive results that will impact FDA policy.

15:05 multi-Platform and Cross-methodological reproducibility of transcriptome Profiling by rna-Seq in the aBrf next-Generation Sequencing Study (aBrf-nGS)Christopher Mason, Ph.D., Assistant Professor, Computational Biomedicine, Weill Cornell Medical College, United StatesWe use standard reference samples to evaluate RNA-Seq across a range of sample quality levels, sample preparation methods and bioinformatics analysis approaches, with results that have the potential to improve the utility and comparability of these various methods and five NGS platforms (Illumina, PacBio, 454, PGM, Proton). Importantly, we demonstrate that even severely degraded RNA, when prepared and analyzed with appropriate methods, can be as useful as intact RNA for sequencing-based quantitative profiling.

15:35 functional Dysregulation in Inflammatory Diseases Carsten O. Daub, Ph.D., Assistant Professor, Biosciences and Nutrition & Science for Life Laboratory, Karolinska Institutet, SwedenEmploying genome-wide expression profiling for contrasting disease and control patients allows not only identification of differentially regulated protein or non-coding transcripts but also inference of the underlying regulatory events.



Genome Informatics Deciphering Disease through Sequencing DataSecond Annual

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Bio-IT World & Cambridge Healthtech Institute’s Fifth ... · Genome Informatics Sequencing Informatics Europe Clinical Genomics ... Challenging translational Bottlenecks Manon van