Cancer gene discovery via network analysis of somatic mutation data. Insuk Lee
|
|
- Phillip Stevens
- 6 years ago
- Views:
Transcription
1 Cancer gene discovery via network analysis of somatic mutation data Insuk Lee
2 Cancer is a progressive genetic disorder. Accumulation of somatic mutations cause cancer. For example, in colorectal cancer, the first gatekeeping mutation (often occur in APC) is followed by series of activation of oncogene and loss-of-function of tumor suppressor genes, which eventually generates a malignant tumor.
3 Sequencing approach to the comprehensive catalog of cancer genes Tumor samples and adjacent healthy tissue (or blood) samples (i.e., matched normal) samples are sequenced (WES) and aligned to identify cancer-associated somatic mutations (and cancer genes). Nat. Rev. Genet 15:556 (2014)
4 Driver vs. Passenger mutations Driver mutation: A mutation that directly or indirectly confers a selective growth advantage to the cell in which it occurs (opposite to passenger mutation) Not all mutations are driver mutations. Therefore, not all genes contain somatic mutations are cancer driver genes. Nature 458:719 (2009)
5 Distinguishing Drivers from Passengers Based on recurrent mutations Use deleteriousness of the mutations
6 Using additional information to reduce false positives Mutation frequency is normalized by gene-specific background mutation rate (BMR), expression level, and replication timing in Mutsig CV. Nature reviews genetics 15:556 (2014)
7 What about cancer genes with low mutation rate? Many hills but only few mountains Of the genomic landscapes of human colorectal cancers (Wood et al. Science 2007) Map of mutations in 11 breast and 11 colorectal cancers. In the landscape, the heights of the peaks reflect the mutation frequency of each gene. A few gene mountains are mutated in a large proportion of tumors: most genes are mutated in <5% of tumors and are represented as hills in the figure. We observed similar distribution of mutation frequency from TCGA data.
8 Long-tail distribution of mutation frequency The majority of the cancer genes are infrequently mutated and have somatic mutations in only few patients, which result in long-tail distribution of mutation frequency. Therefore, methods based on recurrent mutations have intrinsic limitation in cancer gene identification Among 422 known cancer genes by CGC 7 genes: mut in >5% tumors Mutation count genes: mut in >1% tumors 12 genes: no mut in tumors Mutation count TP53 BRAF PTEN IDH1 ATRX APC 200 PIK3CA KMT2D KMT2C ARID1A 0 Mutation distribution across 422 CGC (Cancer Genome Census) genes in 6764 Pan-cancer samples (April 2014 TCGA). 410 mutated genes
9 Cancer is a disease by pathway disorders However, mutations concentrated in known cancer-related pathways, which suggest that pathway-centric approach will be useful in analysis of cancer genomics data. Nat. Rev. Cancer Poster (2002)
10 MUFFINN: mutations for functional impact on network neighbors Predict driver genes based on pathway-level mutational information Genome Biology (2016)
11 3 ways to take account neighbors mutational burden On the following two functional gene networks Genome Res. (2011) Nucleic Acids Res. (2015)
12 Cancer gene sets for benchmarking prediction No comprehensive gold standard cancer gene set We compiled multiple cancer gene sets from various sources of annotations. Each cancer gene set has a different trade-off between accuracy, coverage, and bias. CGC CGC PointMut 20/20 Rules HCD MouseMut 422 genes From CGC (Cancer Genome Census) 118 genes CGC genes which act to cancer via point mutations 124 genes based on the mutational patterns 288 genes High-confidence driver genes by rule-based approach 797 genes Ortholog-mapped genes which are identified by mutagenesis experiment in mice Futreal et al Vogelstein et al Tamborero et al March et al Mann et al. 2012
13 Result 1: MUFFINN performs better than gene-based methods 18 cancer types ~6700 TCGA samples
14 Result 1: MUFFINN performs better than gene-based methods Evaluation based on the all candidates Evaluation based on the top candidates, which go into the follow-up studies
15 Testing significance of using mutational information among indirect network neighbors for MUFFINN Use mutation information of direct neighbors only Use mutation information of all genes
16 Result 2: MUFFINN can predict cancer drivers better with taking only direct neighbors mutational information. GS: Gaussian smoothing IR: Iterative Rank RWR: Random walk with restart
17 Result 3: The larger size of Pan-cancer data makes only marginal improvement in predictions.
18 Result 4: MUFFINN effectively predict cancer genes with only 10% of tumor samples.
19 Manual examination of the novel candidate drivers Selected 199 novel candidate drivers that pass all the following criteria. 1. Predicted in top 1000 by MUFFINN (Prob > 0.5) 2. Predicted in top 1000 by neither Mutsig nor MutationAccessor 3. Annotated by neither CGC nor 20/20 cancer gene sets (to exclude all knowns) Among 199 candidate cancer genes, 128 (64%) genes have direct or indirect supportive evidences in the literatures. Class 1 (11 genes): already reported as cancer genes but not annotated yet by CGC or 20/20 database. Class 2 (14 genes): known to increase cancer susceptibility through germline variants. Class 3 (14 genes): known to be involved in cancer by copy number variation (CNV) or structural variation (SV). Class 4 (89 genes): associated with cancer via expression dysregulation with non-genetic alterations (e.g., epigenetic regulation, mirna target). Class 5 (71 genes): with no evidence (novel candidates to be investigated in the future)
20 Novel candidate drivers with low mutation occurrence have neighboring genes known to be involved in cancer pathways
21 Performing prediction using a companion web server
22 Summary Cancer genome sequencing can facilitate discovery of cancer driver genes. We can distinguish drivers from passengers based on recurrent mutations. Conventional methods based on recurrent mutations are intrinsically limited to the cancer genes with low mutation occurrence. Since cancer is pathway disease, incorporating pathway information will enhance cancer genomics data analysis. We developed a network-based method, MUFFINN, and a companion web server, and demonstrated its superiority in cancer gene prediction. Network-based analysis of cancer genomics data will provide a promising route to the comprehensive catalog of cancer gene.
23 Acknowledgements MUFFINN: cancer gene discovery via network analysis of somatic mutation data Genome Biology 17:129 (June 2016) Yonsei Univeristy, Department of Biotechnology (Korea) Ara Cho, Jung Eun Shim, Eiru Kim EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (Spain) Ben Lehner, Fran Supek
24 Network Biology Lab ( Current members PhD. Jung Eun Shim Sangyoung Lee PhD. Eiru Kim Chan Yeong Kim Tak Lee Muyoung Lee Sunmo Yang Jaewon Cho Kyungsoo Kim Eunbeen Kim Heonjong Han Dasom Bae Former members PhD. Sohyun Hwang PhD. Jawon Song PhD. Jonghoon Lee PhD. Junha Shin PhD. Ara Cho Hongseok Shim PhD. Taeyun Oh PhD. Samuel Beck PhD. Yoonhee Ko PhD. Hanhae Kim PhD. Sungou Ji Hyojin Kim
25
26 Result : Accounting for mutational heterogeneity is not important for MUFFINN.
27 HotNet2 vs. MUFFINN HotNet2 (Nat.Genet. 2015) 1. Assign heat (mutation) to each gene 2. Diffuse heat from hot (highly mutated) to cold genes in the network 3. Extract significantly hot subnetwork (cancer pathway) MUFFINN (this study) 1. Assign heat (mutation) to each gene 2. For each gene, measure mutational burden over network neighbors 3. Rank genes (cancer genes) by the mutational burden
28 Result : HotNet2 and MUFFINN are complementary Retrieval rate for known cancer genes in 144 candidates by HotNet2 and top 144 canddiates by MUFFINN Venn diagram among 422 CGC genes, 144 candidates by HotNet2, and top 144 candidates by MUFFINN
Introduction to Cancer Bioinformatics and cancer biology. Anthony Gitter Cancer Bioinformatics (BMI 826/CS 838) January 20, 2015
Introduction to Cancer Bioinformatics and cancer biology Anthony Gitter Cancer Bioinformatics (BMI 826/CS 838) January 20, 2015 Why cancer bioinformatics? Devastating disease, no cure on the horizon Major
More informationExpanded View Figures
Solip Park & Ben Lehner Epistasis is cancer type specific Molecular Systems Biology Expanded View Figures A B G C D E F H Figure EV1. Epistatic interactions detected in a pan-cancer analysis and saturation
More informationIntegration of Cancer Genome into GECCO- Genetics and Epidemiology of Colorectal Cancer Consortium
Integration of Cancer Genome into GECCO- Genetics and Epidemiology of Colorectal Cancer Consortium Ulrike Peters Fred Hutchinson Cancer Research Center University of Washington U01-CA137088-05, PI: Peters
More informationWhole Genome and Transcriptome Analysis of Anaplastic Meningioma. Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute
Whole Genome and Transcriptome Analysis of Anaplastic Meningioma Patrick Tarpey Cancer Genome Project Wellcome Trust Sanger Institute Outline Anaplastic meningioma compared to other cancers Whole genomes
More informationDavid Tamborero, PhD
David Tamborero, PhD Lopez-Bigas' lab Study of Tumor Genomes Study of Tumor Genomes Study sequencing data of tumors to understand the biological mechanisms shaping the mutational processes observed at
More informationCharacteriza*on of Soma*c Muta*ons in Cancer Genomes
Characteriza*on of Soma*c Muta*ons in Cancer Genomes Ben Raphael Department of Computer Science Center for Computa*onal Molecular Biology Soma*c Muta*ons and Cancer Clonal Theory (Nowell 1976) Passenger
More informationClinical Utility of Actionable Genome Information in Precision Oncology Clinic
Indian Ocean Rim 2017 Laboratory Haematology Congress 2017. 6.18-19, Singapore Clinical Utility of Actionable Genome Information in Precision Oncology Clinic Reimbursement program for NGS panel tests in
More informationProtein Domain-Centric Approach to Study Cancer Somatic Mutations from High-throughput Sequencing Studies
Protein Domain-Centric Approach to Study Cancer Somatic Mutations from High-throughput Sequencing Studies Dr. Maricel G. Kann Assistant Professor Dept of Biological Sciences UMBC 2 The term protein domain
More informationARTICLE RESEARCH. Macmillan Publishers Limited. All rights reserved
Extended Data Figure 6 Annotation of drivers based on clinical characteristics and co-occurrence patterns. a, Putative drivers affecting greater than 10 patients were assessed for enrichment in IGHV mutated
More informationCharacterisation of structural variation in breast. cancer genomes using paired-end sequencing on. the Illumina Genome Analyser
Characterisation of structural variation in breast cancer genomes using paired-end sequencing on the Illumina Genome Analyser Phil Stephens Cancer Genome Project Why is it important to study cancer? Why
More informationAVENIO ctdna Analysis Kits The complete NGS liquid biopsy solution EMPOWER YOUR LAB
Analysis Kits The complete NGS liquid biopsy solution EMPOWER YOUR LAB Analysis Kits Next-generation performance in liquid biopsies 2 Accelerating clinical research From liquid biopsy to next-generation
More informationStructural Variation and Medical Genomics
Structural Variation and Medical Genomics Andrew King Department of Biomedical Informatics July 8, 2014 You already know about small scale genetic mutations Single nucleotide polymorphism (SNPs) Deletions,
More informationIdentifying driver mutations in sequenced cancer genomes: computational approaches to enable precision medicine
Raphael et al. Genome Medicine 2014, 6:5 REVIEW Identifying driver mutations in sequenced cancer genomes: computational approaches to enable precision medicine Benjamin J Raphael 1,2*, Jason R Dobson 1,2,3,
More informationUsing Network Flow to Bridge the Gap between Genotype and Phenotype. Teresa Przytycka NIH / NLM / NCBI
Using Network Flow to Bridge the Gap between Genotype and Phenotype Teresa Przytycka NIH / NLM / NCBI Journal Wisla (1902) Picture from a local fare in Lublin, Poland Genotypes Phenotypes Journal Wisla
More informationSupplementary Figure 1: Comparison of acgh-based and expression-based CNA analysis of tumors from breast cancer GEMMs.
Supplementary Figure 1: Comparison of acgh-based and expression-based CNA analysis of tumors from breast cancer GEMMs. (a) CNA analysis of expression microarray data obtained from 15 tumors in the SV40Tag
More informationACTIVITY 2: EXAMINING CANCER PATIENT DATA
OVERVIEW Refer to the Overview of Cancer Discovery Activities for Key Concepts and Learning Objectives, Curriculum Connections, and Prior Knowledge, as well as background information, references, and additional
More informationCancer troublemakers: a tale of usual suspects and novel villains
Cancer troublemakers: a tale of usual suspects and novel villains Abel González-Pérez and Núria López-Bigas Biomedical Genomics Group Lab web: http://bg.upf.edu Driver genes/mutations: the troublemakers
More informatione-driver: A novel method to identify protein regions driving cancer Eduard Porta-Pardo 1, Adam Godzik 1,* 1
Original Paper e-driver: A novel method to identify protein regions driving cancer Eduard Porta-Pardo 1, Adam Godzik 1,* 1 Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute,
More informationUnderstanding Genotype- Phenotype relations in Cancer via Network Approaches
AlgoCSB Algorithmic Methods in Computational and Systems Biology Understanding Genotype- Phenotype relations in Cancer via Network Approaches Teresa Przytycka NIH / NLM / NCBI Phenotypes Journal Wisla
More informationSession 4 Rebecca Poulos
The Cancer Genome Atlas (TCGA) & International Cancer Genome Consortium (ICGC) Session 4 Rebecca Poulos Prince of Wales Clinical School Introductory bioinformatics for human genomics workshop, UNSW 20
More informationClinical significance of genetic analysis in glioblastoma treatment
Clinical significance of genetic analysis in glioblastoma treatment Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Koji Yoshimoto Can we get prognostic
More informationPlasma-Seq conducted with blood from male individuals without cancer.
Supplementary Figures Supplementary Figure 1 Plasma-Seq conducted with blood from male individuals without cancer. Copy number patterns established from plasma samples of male individuals without cancer
More informationDGPathinter: a novel model for identifying driver genes via knowledge-driven matrix factorization with prior knowledge from interactome and pathways
DGPathinter: a novel model for identifying driver genes via knowledge-driven matrix factorization with prior knowledge from interactome and pathways Jianing Xi, *, Minghui Wang,2, * and Ao Li,2 School
More informationSession 6: Integration of epigenetic data. Peter J Park Department of Biomedical Informatics Harvard Medical School July 18-19, 2016
Session 6: Integration of epigenetic data Peter J Park Department of Biomedical Informatics Harvard Medical School July 18-19, 2016 Utilizing complimentary datasets Frequent mutations in chromatin regulators
More informationNGS in tissue and liquid biopsy
NGS in tissue and liquid biopsy Ana Vivancos, PhD Referencias So, why NGS in the clinics? 2000 Sanger Sequencing (1977-) 2016 NGS (2006-) ABIPrism (Applied Biosystems) Up to 2304 per day (96 sequences
More informationFrequency(%) KRAS G12 KRAS G13 KRAS A146 KRAS Q61 KRAS K117N PIK3CA H1047 PIK3CA E545 PIK3CA E542K PIK3CA Q546. EGFR exon19 NFS-indel EGFR L858R
Frequency(%) 1 a b ALK FS-indel ALK R1Q HRAS Q61R HRAS G13R IDH R17K IDH R14Q MET exon14 SS-indel KIT D8Y KIT L76P KIT exon11 NFS-indel SMAD4 R361 IDH1 R13 CTNNB1 S37 CTNNB1 S4 AKT1 E17K ERBB D769H ERBB
More informationCOMPUTATIONAL OPTIMISATION OF TARGETED DNA SEQUENCING FOR CANCER DETECTION
COMPUTATIONAL OPTIMISATION OF TARGETED DNA SEQUENCING FOR CANCER DETECTION Pierre Martinez, Nicholas McGranahan, Nicolai Juul Birkbak, Marco Gerlinger, Charles Swanton* SUPPLEMENTARY INFORMATION SUPPLEMENTARY
More informationSupplementary Figure 1
Supplementary Figure 1 An example of the gene-term-disease network automatically generated by Phenolyzer web server for 'autism'. The largest word represents the user s input term, Autism. The pink round
More informationNGS in Cancer Pathology After the Microscope: From Nucleic Acid to Interpretation
NGS in Cancer Pathology After the Microscope: From Nucleic Acid to Interpretation Michael R. Rossi, PhD, FACMG Assistant Professor Division of Cancer Biology, Department of Radiation Oncology Department
More informationPersonalised medicine: Past, present and future
Kathmandu, Bir Hospital visit, August 2018 Personalised medicine: Past, present and future Rodney J. Scott University of Newcastle, NSW, Australia & Hunter Area Pathology Service Current Medical Care Started
More informationNetwork-assisted data analysis
Network-assisted data analysis Bing Zhang Department of Biomedical Informatics Vanderbilt University bing.zhang@vanderbilt.edu Protein identification in shotgun proteomics Protein digestion LC-MS/MS Protein
More information38 Int'l Conf. Bioinformatics and Computational Biology BIOCOMP'16
38 Int'l Conf. Bioinformatics and Computational Biology BIOCOMP'16 PGAR: ASD Candidate Gene Prioritization System Using Expression Patterns Steven Cogill and Liangjiang Wang Department of Genetics and
More information2013 Holiday Lectures on Science Medicine in the Genomic Era
This educator guide provides support for two Cancer Discovery activities, both based on a Howard Hughes Medical Institute 2013 Holiday Lectures on Science video featuring researcher Dr. Charles L. Sawyers.
More informationSupplementary Figure 1. Estimation of tumour content
Supplementary Figure 1. Estimation of tumour content a, Approach used to estimate the tumour content in S13T1/T2, S6T1/T2, S3T1/T2 and S12T1/T2. Tissue and tumour areas were evaluated by two independent
More informationVariant interpretation exercise. ACGS Somatic Variant Interpretation Workshop Joanne Mason 21/09/18
Variant interpretation exercise ACGS Somatic Variant Interpretation Workshop Joanne Mason 21/09/18 Format of exercise Compile a list of tricky variants across solid cancer and haematological malignancy.
More informationGlioblastoma pathophysiology: or a
Glioblastoma pathophysiology: A or a? M.J. van den Bent The Brain Tumor Center at Erasmus MC Cancer Center Rotterdam, the Netherlands Pathophysiology: pathophysiology seeks to explain the physiological
More informationNature Getetics: doi: /ng.3471
Supplementary Figure 1 Summary of exome sequencing data. ( a ) Exome tumor normal sample sizes for bladder cancer (BLCA), breast cancer (BRCA), carcinoid (CARC), chronic lymphocytic leukemia (CLLX), colorectal
More informationThe Role of Next Generation Sequencing in Solid Tumor Mutation Testing
The Role of Next Generation Sequencing in Solid Tumor Mutation Testing Allie H. Grossmann MD PhD Department of Pathology, University of Utah Division of Anatomic Pathology & Oncology, ARUP Laboratories
More informationSUPPLEMENTARY INFORMATION. Intron retention is a widespread mechanism of tumor suppressor inactivation.
SUPPLEMENTARY INFORMATION Intron retention is a widespread mechanism of tumor suppressor inactivation. Hyunchul Jung 1,2,3, Donghoon Lee 1,4, Jongkeun Lee 1,5, Donghyun Park 2,6, Yeon Jeong Kim 2,6, Woong-Yang
More informationMutational Impact on Diagnostic and Prognostic Evaluation of MDS
Mutational Impact on Diagnostic and Prognostic Evaluation of MDS Elsa Bernard, PhD Papaemmanuil Lab, Computational Oncology, MSKCC MDS Foundation ASH 2018 Symposium Disclosure Research funds provided by
More informationThe Cancer Genome Atlas Pan-cancer analysis Katherine A. Hoadley
The Cancer Genome Atlas Pan-cancer analysis Katherine A. Hoadley Department of Genetics Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill What is TCGA? The Cancer Genome
More informationAD (Leave blank) TITLE: Genomic Characterization of Brain Metastasis in Non-Small Cell Lung Cancer Patients
AD (Leave blank) Award Number: W81XWH-12-1-0444 TITLE: Genomic Characterization of Brain Metastasis in Non-Small Cell Lung Cancer Patients PRINCIPAL INVESTIGATOR: Mark A. Watson, MD PhD CONTRACTING ORGANIZATION:
More informationMolecular Subtyping of Endometrial Cancer: A ProMisE ing Change
Molecular Subtyping of Endometrial Cancer: A ProMisE ing Change Charles Matthew Quick, M.D. Associate Professor of Pathology Director of Gynecologic Pathology University of Arkansas for Medical Sciences
More informationAdvances in Brain Tumor Research: Leveraging BIG data for BIG discoveries
Advances in Brain Tumor Research: Leveraging BIG data for BIG discoveries Jill Barnholtz-Sloan, PhD Associate Professor & Associate Director for Bioinformatics and Translational Informatics jsb42@case.edu
More informationNew Drug development and Personalized Therapy in The Era of Molecular Medicine
New Drug development and Personalized Therapy in The Era of Molecular Medicine Ramesh K. Ramanathan MD Virginia G. Piper Cancer Center Translational Genomics Research Institute Scottsdale, AZ Clinical
More informationCancer Gene Panels. Dr. Andreas Scherer. Dr. Andreas Scherer President and CEO Golden Helix, Inc. Twitter: andreasscherer
Cancer Gene Panels Dr. Andreas Scherer Dr. Andreas Scherer President and CEO Golden Helix, Inc. scherer@goldenhelix.com Twitter: andreasscherer About Golden Helix - Founded in 1998 - Main outside investor:
More informationSupplementary Tables. Supplementary Figures
Supplementary Files for Zehir, Benayed et al. Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients Supplementary Tables Supplementary Table 1: Sample
More informationGenomic tests to personalize therapy of metastatic breast cancers. Fabrice ANDRE Gustave Roussy Villejuif, France
Genomic tests to personalize therapy of metastatic breast cancers Fabrice ANDRE Gustave Roussy Villejuif, France Future application of genomics: Understand the biology at the individual scale Patients
More informationGolden Helix s End-to-End Solution for Clinical Labs
Golden Helix s End-to-End Solution for Clinical Labs Steven Hystad - Field Application Scientist Nathan Fortier Senior Software Engineer 20 most promising Biotech Technology Providers Top 10 Analytics
More informationInsights from Sequencing the Melanoma Exome
Insights from Sequencing the Melanoma Exome Michael Krauthammer, MD PhD, December 2 2015 Yale University School Yof Medicine 1 2012 Exome Screens and Results Exome Sequencing of 108 sun-exposed melanomas
More informationCorporate Medical Policy Genetic Testing for Cutaneous Malignant Melanoma
Corporate Medical Policy Genetic Testing for Cutaneous Malignant Melanoma File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_cutaneous_malignant_melanoma 8/2011
More informationPrecision Genetic Testing in Cancer Treatment and Prognosis
Precision Genetic Testing in Cancer Treatment and Prognosis Deborah Cragun, PhD, MS, CGC Genetic Counseling Graduate Program Director University of South Florida Case #1 Diana is a 47 year old cancer patient
More informationThe Cancer Genome Atlas & International Cancer Genome Consortium
The Cancer Genome Atlas & International Cancer Genome Consortium Session 3 Dr Jason Wong Prince of Wales Clinical School Introductory bioinformatics for human genomics workshop, UNSW 31 st July 2014 1
More informationAhrim Youn 1,2, Kyung In Kim 2, Raul Rabadan 3,4, Benjamin Tycko 5, Yufeng Shen 3,4,6 and Shuang Wang 1*
Youn et al. BMC Medical Genomics (2018) 11:98 https://doi.org/10.1186/s12920-018-0425-z RESEARCH ARTICLE Open Access A pan-cancer analysis of driver gene mutations, DNA methylation and gene expressions
More informationSession 4 Rebecca Poulos
The Cancer Genome Atlas (TCGA) & International Cancer Genome Consortium (ICGC) Session 4 Rebecca Poulos Prince of Wales Clinical School Introductory bioinformatics for human genomics workshop, UNSW 28
More informationAVENIO family of NGS oncology assays ctdna and Tumor Tissue Analysis Kits
AVENIO family of NGS oncology assays ctdna and Tumor Tissue Analysis Kits Accelerating clinical research Next-generation sequencing (NGS) has the ability to interrogate many different genes and detect
More informationPrecision medicine: How to exploit the growing knowledge on the evolving genomes of cells to improve cancer prevention and therapy.
Precision medicine: How to exploit the growing knowledge on the evolving genomes of cells to improve cancer prevention and therapy Joe Costello, PhD Department of Neurological Surgery A more accurate and
More informationIntelliGENSM. Integrated Oncology is making next generation sequencing faster and more accessible to the oncology community.
IntelliGENSM Integrated Oncology is making next generation sequencing faster and more accessible to the oncology community. NGS TRANSFORMS GENOMIC TESTING Background Cancers may emerge as a result of somatically
More informationReporting TP53 gene analysis results in CLL
Reporting TP53 gene analysis results in CLL Mutations in TP53 - From discovery to clinical practice in CLL Discovery Validation Clinical practice Variant diversity *Leroy at al, Cancer Research Review
More informationCOSMIC - Catalogue of Somatic Mutations in Cancer
COSMIC - Catalogue of Somatic Mutations in Cancer http://cancer.sanger.ac.uk/cosmic https://academic.oup.com/nar/articl e-lookup/doi/10.1093/nar/gkw1121 Data In Large-scale systematic screens Detailed
More informationSupplementary Figure 1. Schematic diagram of o2n-seq. Double-stranded DNA was sheared, end-repaired, and underwent A-tailing by standard protocols.
Supplementary Figure 1. Schematic diagram of o2n-seq. Double-stranded DNA was sheared, end-repaired, and underwent A-tailing by standard protocols. A-tailed DNA was ligated to T-tailed dutp adapters, circularized
More informationPatient networks! in cancer:! a platform for data integration
Anna Goldenberg and The Goldenberg Lab Patient networks! in cancer:! a platform for data integration Outline o Data integra-on problem setup o Pa-ent network representa-on why and how o Similarity Network
More informationMolEcular Taxonomy of BReast cancer International Consortium (METABRIC)
PERSPECTIVE 1 LARGE SCALE DATASET EXAMPLES MolEcular Taxonomy of BReast cancer International Consortium (METABRIC) BC Cancer Agency, Vancouver Samuel Aparicio, PhD FRCPath Nan and Lorraine Robertson Chair
More informationAccel-Amplicon Panels
Accel-Amplicon Panels Amplicon sequencing has emerged as a reliable, cost-effective method for ultra-deep targeted sequencing. This highly adaptable approach is especially applicable for in-depth interrogation
More informationBiology of cancer development in the GI tract
1 Genesis and progression of GI cancer a genetic disease Colorectal cancer Fearon and Vogelstein proposed a genetic model to explain the stepwise formation of colorectal cancer (CRC) from normal colonic
More informationTrinity: Transcriptome Assembly for Genetic and Functional Analysis of Cancer [U24]
Trinity: Transcriptome Assembly for Genetic and Functional Analysis of Cancer [U24] ITCR meeting, June 2016 The Cancer Transcriptome A window into the (expressed) genetic and epigenetic state of a tumor
More informationDr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory
Dr Yvonne Wallis Consultant Clinical Scientist West Midlands Regional Genetics Laboratory Personalised Therapy/Precision Medicine Selection of a therapeutic drug based on the presence or absence of a specific
More informationGenome. Institute. GenomeVIP: A Genomics Analysis Pipeline for Cloud Computing with Germline and Somatic Calling on Amazon s Cloud. R. Jay Mashl.
GenomeVIP: the Genome Institute at Washington University A Genomics Analysis Pipeline for Cloud Computing with Germline and Somatic Calling on Amazon s Cloud R. Jay Mashl October 20, 2014 Turnkey Variant
More informationVisualization and interpretation of cancer data using linked micromap plots
Journal of the Korean Data & Information Science Society 2014, 25(6), 1531 1538 http://dx.doi.org/10.7465/jkdi.2014.25.6.1531 한국데이터정보과학회지 Visualization and interpretation of cancer data using linked micromap
More informationComputer Science, Biology, and Biomedical Informatics (CoSBBI) Outline. Molecular Biology of Cancer AND. Goals/Expectations. David Boone 7/1/2015
Goals/Expectations Computer Science, Biology, and Biomedical (CoSBBI) We want to excite you about the world of computer science, biology, and biomedical informatics. Experience what it is like to be a
More informationStatistical analysis of RIM data (retroviral insertional mutagenesis) Bioinformatics and Statistics The Netherlands Cancer Institute Amsterdam
Statistical analysis of RIM data (retroviral insertional mutagenesis) Lodewyk Wessels Bioinformatics and Statistics The Netherlands Cancer Institute Amsterdam Viral integration Viral integration Viral
More informationNature Genetics: doi: /ng Supplementary Figure 1. Mutational signatures in BCC compared to melanoma.
Supplementary Figure 1 Mutational signatures in BCC compared to melanoma. (a) The effect of transcription-coupled repair as a function of gene expression in BCC. Tumor type specific gene expression levels
More informationComprehensive Analyses of Circulating Cell- Free Tumor DNA
Comprehensive Analyses of Circulating Cell- Free Tumor DNA Boston, MA June 28th, 2016 Derek Murphy, Ph.D. Scientist, Research and Development Personal Genome Diagnostics Acquisition of Somatic Alterations
More informationAnalysis of Massively Parallel Sequencing Data Application of Illumina Sequencing to the Genetics of Human Cancers
Analysis of Massively Parallel Sequencing Data Application of Illumina Sequencing to the Genetics of Human Cancers Gordon Blackshields Senior Bioinformatician Source BioScience 1 To Cancer Genetics Studies
More informationDecades of cancer research have demonstrated that. Computational approaches for the identification of cancer genes and pathways
Computational approaches for the identification of cancer genes and pathways Christos M. Dimitrakopoulos 1,2 and Niko Beerenwinkel 1,2 * High-throughput DNA sequencing techniques enable large-scale measurement
More informationGenomic landsccape of poorly differentiated and anaplastic thyroid carcinomas: Clues for better classification, risk stratification and therapy
ACCME/Disclosures The USCAP requires that anyone in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner
More informationFrom pathology research to stratified medicine trials
From pathology research to stratified medicine trials Dr. John Bartlett Program Director Transformative Pathology C CCTG Breast Group Steering Committee ASCO-CAP HER2 Panel As is your Pathology, so is
More informationVertical Magnetic Separation of Circulating Tumor Cells and Somatic Genomic-Alteration Analysis in Lung Cancer Patients
Vertical Magnetic Separation of Circulating Cells and Somatic Genomic-Alteration Analysis in Lung Cancer Patients Chang Eun Yoo 1,2#, Jong-Myeon Park 3#, Hui-Sung Moon 1,2, Je-Gun Joung 2, Dae-Soon Son
More informationBWA alignment to reference transcriptome and genome. Convert transcriptome mappings back to genome space
Whole genome sequencing Whole exome sequencing BWA alignment to reference transcriptome and genome Convert transcriptome mappings back to genome space genomes Filter on MQ, distance, Cigar string Annotate
More informationCancer Genomes How to Analyze Your Own Genome
Cancer Genomes 02-223 How to Analyze Your Own Genome Cancer vs. Heritable Diseases So far, we mostly discussed heritable diseases, where the disease causing mutaaons are inherited from one individual to
More informationIdentification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins
Identification and clinical detection of genetic alterations of pre-neoplastic lesions Time for the PML ome? David Sidransky MD Johns Hopkins February 3-5, 2016 Lansdowne Resort, Leesburg, VA Molecular
More informationTen years ago, the idea that all of the genes
REVIEW Cancer Genome Landscapes Bert Vogelstein, Nickolas Papadopoulos, Victor E. Velculescu, Shibin Zhou, Luis A. Diaz Jr., Kenneth W. Kinzler* Over the past decade, comprehensive sequencing efforts have
More informationLiposarcoma*Genome*Project*
LiposarcomaGenomeProject July2015! Submittedby: JohnMullen,MD EdwinChoy,MD,PhD GregoryCote,MD,PhD G.PeturNielsen,MD BradBernstein,MD,PhD Liposarcoma Background Liposarcoma is the most common soft tissue
More informationThe 100,000 Genomes Project Harnessing the power of genomics for NHS rare disease and cancer patients
The 100,000 Genomes Project Harnessing the power of genomics for NHS rare disease and cancer patients Dr Richard Scott, Clinical Lead for Rare Disease Dr Nirupa Murugaesu, Clinical Lead for Cancer Four
More informationCirculating Tumor DNA in GIST and its Implications on Treatment
Circulating Tumor DNA in GIST and its Implications on Treatment October 2 nd 2017 Dr. Ciara Kelly Assistant Attending Physician Sarcoma Medical Oncology Service Objectives Background Liquid biopsy & ctdna
More informationKRAS: ONE ACTOR, MANY POTENTIAL ROLES IN DIAGNOSIS
UNIVERSITÀ DEGLI STUDI DI PALERMO Scuola di Specializzazione in Biochimica Clinica Direttore Prof. Marcello Ciaccio KRAS: ONE ACTOR, MANY POTENTIAL ROLES IN DIAGNOSIS Loredana Bruno KRAS gene Proto-oncogene
More informationSimultaneous Identification of Multiple Driver Pathways in Cancer
Simultaneous Identification of Multiple Driver Pathways in Cancer Mark D. M. Leiserson 1, Dima Blokh 2, Roded Sharan 2., Benjamin J. Raphael 1. * 1 Department of Computer Science and Center for Computational
More informationThe lymphoma-associated NPM-ALK oncogene elicits a p16ink4a/prb-dependent tumor-suppressive pathway. Blood Jun 16;117(24):
DNA Sequencing Publications Standard Sequencing 1 Carro MS et al. DEK Expression is controlled by E2F and deregulated in diverse tumor types. Cell Cycle. 2006 Jun;5(11) 2 Lassandro L et al. The DNA sequence
More informationHuman Genetics 542 Winter 2018 Syllabus
Human Genetics 542 Winter 2018 Syllabus Monday, Wednesday, and Friday 9 10 a.m. 5915 Buhl Course Director: Tony Antonellis Jan 3 rd Wed Mapping disease genes I: inheritance patterns and linkage analysis
More informationCorporate Medical Policy
Corporate Medical Policy Molecular Panel Testing of Cancers to Identify Targeted Therapies File Name: Origination: Last CAP Review: Next CAP Review: Last Review: molecular_panel_testing_of_cancers_to_identify_targeted_therapies
More informationGenetic alterations of histone lysine methyltransferases and their significance in breast cancer
Genetic alterations of histone lysine methyltransferases and their significance in breast cancer Supplementary Materials and Methods Phylogenetic tree of the HMT superfamily The phylogeny outlined in the
More informationCancer Treatment and Research
Cancer Treatment and Research Volume 155 Series Editor Steven T. Rosen For further volumes: http://www.springer.com/series/5808 Boris Pasche Editor Cancer Genetics 123 Editor Boris Pasche, MD, PhD, FACP
More informationNext generation histopathological diagnosis for precision medicine in solid cancers
Next generation histopathological diagnosis for precision medicine in solid cancers from genomics to clinical application Aldo Scarpa ARC-NET Applied Research on Cancer Department of Pathology and Diagnostics
More informationIdentification of heritable genetic risk factors for bladder cancer through genome-wide association studies (GWAS)
BCAN 2014 August 9, 2014 Identification of heritable genetic risk factors for bladder cancer through genome-wide association studies (GWAS) Ludmila Prokunina-Olsson, PhD Investigator Laboratory of Translational
More informationHuman Genetics 542 Winter 2017 Syllabus
Human Genetics 542 Winter 2017 Syllabus Monday, Wednesday, and Friday 9 10 a.m. 5915 Buhl Course Director: Tony Antonellis Module I: Mapping and characterizing simple genetic diseases Jan 4 th Wed Mapping
More informationThe mutations that drive cancer. Paul Edwards. Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge
The mutations that drive cancer Paul Edwards Department of Pathology and Cancer Research UK Cambridge Institute, University of Cambridge Previously on Cancer... hereditary predisposition Normal Cell Slightly
More informationShould novel molecular therapies replace old knowledge of clinical tumor biology?
Should novel molecular therapies replace old knowledge of clinical tumor biology? Danai Daliani, M.D. Director, 1 st Oncology Clinic Euroclinic of Athens Cancer Treatments Localized disease Surgery XRT
More informationAre there the specific prognostic factors for triplenegative subtype of early breast cancers (pt1-2n0m0)?
Are there the specific prognostic factors for triplenegative subtype of early breast cancers (pt1-2n0m0)? Department of General Surgery, Anam Hospital, Korea University, College of Medicine, 126-, Anam-dong
More informationThe feasibility of circulating tumour DNA as an alternative to biopsy for mutational characterization in Stage III melanoma patients
The feasibility of circulating tumour DNA as an alternative to biopsy for mutational characterization in Stage III melanoma patients ASSC Scientific Meeting 13 th October 2016 Prof Andrew Barbour UQ SOM
More informationSupplementary Materials for
www.sciencetranslationalmedicine.org/cgi/content/full/7/283/283ra54/dc1 Supplementary Materials for Clonal status of actionable driver events and the timing of mutational processes in cancer evolution
More information