Omics-based Medicine and Systems Pathology

OBJECTIVES Recent important advances in the human genomics and post-genomic "omics" are now bringing about a new medical care which we call "omics-based medicine". In this article, we investigated the development and future possibilities of omics-based medicine. METHODS We divided the development of omics-based medicine into three generations in order to clarify the main clinical goals and characteristics of informatics method of each generation, together with its future possibilities. RESULTS The first generation of omics-based medicine started with "genomic medicine" based on the inborn individual differences of genome. It has opened the study of genetic polymorphism of the diseases and promoted the personalized medication based on the pharmacogenetic/pharmacogenomic difference of the drug response. In the second generation of omics-based medicine, owing to the advances in the high-throughput technology, vast amount of the various post-genomic disease omics data containing comprehensive molecular information of diseased somatic cells has become available. It reflects the ongoing state of diseases more closely and enables the predictive medicine such as prognosis prediction of disease by applying the data-driven analysis. Finally, due to the rapidly growing knowledge about the cellular molecular network, system-level understanding of the disease, called systems pathology, becomes possible. It can fully exploit the substantial contents of disease omics and will lead to a comprehensive understanding of disease process by using model-driven analysis. CONCLUSION Omics-based medicine and systems pathology will realize a new personalized and predictive medicine.

[1]  P. Tartter,et al.  Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? , 2008, American journal of surgery.

[2]  Pardis C Sabeti,et al.  Linkage disequilibrium in the human genome , 2001, Nature.

[3]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[4]  S. P. Fodor,et al.  Multiplexed biochemical assays with biological chips , 1993, Nature.

[5]  D. Edwards Introduction to graphical modelling , 1995 .

[6]  R. Stoughton,et al.  Experimental annotation of the human genome using microarray technology , 2001, Nature.

[7]  Hiroshi Tanaka,et al.  Inferring within-patient HIV-1 evolutionary dynamics under anti-HIV therapy using serial virus samples with vSPA , 2009, BMC Bioinformatics.

[8]  Hiroshi Tanaka,et al.  Surgical contribution to recurrence-free survival in patients with macrovascular-invasion-negative hepatocellular carcinoma. , 2009, Journal of the American College of Surgeons.

[9]  Hiroshi Tanaka,et al.  Longitudinal phylogenetic tree of within-host viral evolution from noncontemporaneous samples: a distance-based sequential-linking method. , 2003, Gene.

[10]  J. Stec,et al.  Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Francis S. Collins,et al.  Genomic medicine--a primer. , 2002, The New England journal of medicine.

[12]  T. Frayling Genome–wide association studies provide new insights into type 2 diabetes aetiology , 2007, Nature Reviews Genetics.

[13]  J. Baselga Clinical trials of Herceptin(trastuzumab). , 2001, European journal of cancer.

[14]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[15]  A. Young,et al.  A polymorphic DNA marker genetically linked to Huntington's disease , 1983, Nature.

[16]  Toshihiro Tanaka The International HapMap Project , 2003, Nature.

[17]  Eric P. Hoffman,et al.  Dystrophin: The protein product of the duchenne muscular dystrophy locus , 1987, Cell.

[18]  T. Hirano Cytokines in autoimmune disease and chronic inflammatory proliferative disease. , 2002, Cytokine & growth factor reviews.

[19]  Koichi Tanaka,et al.  Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry , 1988 .

[20]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[21]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  E. Petricoin,et al.  Clinical Application of Proteomics in Ovarian Cancer Prevention and Treatment , 2012, Molecular Diagnosis & Therapy.

[23]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[24]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[25]  L. Hood,et al.  Systems medicine: the future of medical genomics and healthcare , 2009, Genome Medicine.

[26]  L. Almasy,et al.  Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes , 2007, Nature Genetics.

[27]  E. Petricoin,et al.  Use of proteomic patterns in serum to identify ovarian cancer , 2002, The Lancet.

[28]  D. Kwiatkowski,et al.  Perturbation Analysis: A Simple Method for Filtering SNPs with Erroneous Genotyping in Genome‐Wide Association Studies , 2008, Annals of human genetics.

[29]  S. Averbuch,et al.  Gefitinib (‘Iressa’, ZD1839) and new epidermal growth factor receptor inhibitors , 2004, British Journal of Cancer.

[30]  D J Schaid,et al.  Genotype relative risks: methods for design and analysis of candidate-gene association studies. , 1993, American journal of human genetics.

[31]  Dhavendra Kumar,et al.  Genomic medicine: a new frontier of medicine in the twenty first century , 2007, Genomic Medicine.

[32]  C. Ponting,et al.  Finishing the euchromatic sequence of the human genome , 2004 .

[33]  Nir Friedman,et al.  Being Bayesian about Network Structure , 2000, UAI.

[34]  R Haux,et al.  Towards Clinical Bioinformatics: Advancing Genomic Medicine with Informatics Methods and Tools , 2004, Methods of Information in Medicine.

[35]  Rainer Spang,et al.  Inferring cellular networks – a review , 2007, BMC Bioinformatics.

[36]  Subin Mary Zachariah,et al.  Pharmacogenomics: The Right Drug to the Right Person , 2009, Journal of clinical medicine research.

[37]  Y. Xing,et al.  Probe Selection and Expression Index Computation of Affymetrix Exon Arrays , 2006, PloS one.

[38]  A. Rodrigo,et al.  Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA. , 2000, Molecular biology and evolution.

[39]  Chris Wiggins,et al.  ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context , 2004, BMC Bioinformatics.

[40]  Marcia M. Nizzari,et al.  Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels , 2007, Science.

[41]  Age K Smilde,et al.  Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis , 2007, Genome Biology.

[42]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[43]  J. Weinstein Fishing expeditions [6] , 1998 .

[44]  Syed Mohsin,et al.  Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer , 2003, The Lancet.

[45]  P. Corey,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 2012 .

[46]  T. Ideker,et al.  Network-based classification of breast cancer metastasis , 2007, Molecular systems biology.

[47]  William C Hahn,et al.  Functional genetics and experimental models of human cancer. , 2004, Trends in molecular medicine.

[48]  H. Kitano Computational systems biology , 2002, Nature.

[49]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[50]  Michael E Phelps,et al.  Systems Biology and New Technologies Enable Predictive and Preventative Medicine , 2004, Science.

[51]  Andy Gaughan Bridging the divide: the need for translational informatics. , 2006, Pharmacogenomics.

[52]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[53]  M. Relling,et al.  Moving towards individualized medicine with pharmacogenomics , 2004, Nature.

[54]  Adam A. Margolin,et al.  Reverse engineering of regulatory networks in human B cells , 2005, Nature Genetics.

[55]  A. Singleton,et al.  Genomewide association studies and human disease. , 2009, The New England journal of medicine.

[56]  M. Rubin,et al.  Pathway biomarker profiling of localized and metastatic human prostate cancer reveal metastatic and prognostic signatures. , 2009, Journal of proteome research.

[57]  Cole Trapnell,et al.  How to map billions of short reads onto genomes , 2009, Nature Biotechnology.

[58]  E. Wang,et al.  Genetic studies of diseases , 2007, Cellular and Molecular Life Sciences.

[59]  Hiroshi Tanaka Bioinformatics and genomics for opening new perspective for personalized care. , 2008, Studies in health technology and informatics.

[60]  E. Schiffrin Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. , 2004, American journal of hypertension.

[61]  J. Weinstein 'Omic' and hypothesis-driven research in the molecular pharmacology of cancer. , 2002, Current opinion in pharmacology.

[62]  Hiroshi Tanaka,et al.  Research and education for biomedical informatics at Tokyo Medical and Dental University. , 2007, Yearbook of medical informatics.

[63]  Elske Ammenwerth,et al.  Towards clinical bioinformatics: Advancing genomic medicine with informatics methods and tools - Findings from the IMIA Yearbook of Medical Informatics 2004 , 2004 .

[64]  L. Staudt,et al.  The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. , 2002, The New England journal of medicine.

[65]  T. Yip,et al.  New desorption strategies for the mass spectrometric analysis of macromolecules , 1993 .

[66]  M. Nishimura,et al.  A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations , 2006, British Journal of Cancer.

[67]  M. Nowak,et al.  Dynamics of cancer progression , 2004, Nature Reviews Cancer.

[68]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[69]  Eric E. Schadt,et al.  Moving toward a system genetics view of disease , 2007, Mammalian Genome.

[70]  Raghu Kalluri,et al.  The epithelial–mesenchymal transition: new insights in signaling, development, and disease , 2006, The Journal of cell biology.

[71]  L. Tsui,et al.  Identification of the cystic fibrosis gene: chromosome walking and jumping. , 1989, Science.

[72]  Dan M Roden,et al.  Genetic determinants of response to warfarin during initial anticoagulation. , 2008, The New England journal of medicine.

[73]  J. Ross,et al.  MammaPrint™ 70-gene signature: another milestone in personalized medical care for breast cancer patients , 2009, Expert review of molecular diagnostics.

[74]  S Fuhrman,et al.  Reveal, a general reverse engineering algorithm for inference of genetic network architectures. , 1998, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[75]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[76]  Michal Linial,et al.  Using Bayesian Networks to Analyze Expression Data , 2000, J. Comput. Biol..

[77]  I S Kohane,et al.  Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements. , 1999, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[78]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[79]  Hiroaki Kitano,et al.  Structure of Protein Interaction Networks and Their Implications on Drug Design , 2009, PLoS Comput. Biol..