Promise of personalized omics to precision medicine

The rapid development of high‐throughput technologies and computational frameworks enables the examination of biological systems in unprecedented detail. The ability to study biological phenomena at omics levels in turn is expected to lead to significant advances in personalized and precision medicine. Patients can be treated according to their own molecular characteristics. Individual omes as well as the integrated profiles of multiple omes, such as the genome, the epigenome, the transcriptome, the proteome, the metabolome, the antibodyome, and other omics information are expected to be valuable for health monitoring, preventative measures, and precision medicine. Moreover, omics technologies have the potential to transform medicine from traditional symptom‐oriented diagnosis and treatment of diseases toward disease prevention and early diagnostics. We discuss here the advances and challenges in systems biology‐powered personalized medicine at its current stage, as well as a prospective view of future personalized health care at the end of this review. WIREs Syst Biol Med 2013, 5:73–82. doi: 10.1002/wsbm.1198

[1]  A. Y. Lu,et al.  Pharmacogenetics, Pharmacogenomics, and Individualized Medicine , 2011, Pharmacological Reviews.

[2]  Inyoul Lee,et al.  Extracellular microRNA: a new source of biomarkers. , 2011, Mutation research.

[3]  Euan A Ashley,et al.  Performance comparison of whole-genome sequencing platforms , 2011, Nature Biotechnology.

[4]  C. Newgard.  Interplay between lipids and branched-chain amino acids in development of insulin resistance. , 2012, Cell metabolism.

[5]  J. Barrett,et al.  Genetic risk prediction in complex disease , 2011, Human molecular genetics.

[6]  Andrew C. Adey,et al.  Haplotype-resolved genome sequencing of a Gujarati Indian individual , 2011, Nature Biotechnology.

[7]  John C Lindon,et al.  Pharmacometabonomics as an effector for personalized medicine. , 2011, Pharmacogenomics.

[8]  Y. Louzoun,et al.  Rep‐Seq: uncovering the immunological repertoire through next‐generation sequencing , 2012, Immunology.

[9]  Jan Tavernier,et al.  Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors , 2011, Nature Medicine.

[10]  C. Mayr,et al.  Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells , 2009, Cell.

[11]  David T. W. Jones,et al.  Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma , 2012, Nature.

[12]  T. Hankemeier,et al.  Metabolomics-based systems biology and personalized medicine: moving towards n = 1 clinical trials? , 2006, Pharmacogenomics.

[13]  A. Barabasi,et al.  Systems biology and the future of medicine , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[14]  Huanming Yang,et al.  Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm , 2012, Cell.

[15]  Benjamin J. Raphael,et al.  Integrated Genomic Analyses of Ovarian Carcinoma , 2011, Nature.

[16]  Richard B. Schwab,et al.  Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens , 2012, Nucleic acids research.

[17]  David T. W. Jones,et al.  Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations , 2012, Cell.

[18]  Alexander A. Morgan,et al.  Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases , 2012, PLoS genetics.

[19]  Richard M Caprioli,et al.  A Novel Histology-directed Strategy for MALDI-MS Tissue Profiling That Improves Throughput and Cellular Specificity in Human Breast Cancer* , 2006, Molecular & Cellular Proteomics.

[20]  Joseph B. Martin.  Huntington's disease , 1984, Neurology.

[21]  M. Gerstein,et al.  The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing , 2008, Science.

[22]  Y. Lee,et al.  Gene-Gene and Gene-Environmental Interactions of Childhood Asthma: A Multifactor Dimension Reduction Approach , 2012, PloS one.

[23]  V. Hu,et al.  A systems approach towards an understanding, diagnosis and personalized treatment of autism spectrum disorders. , 2011, Pharmacogenomics.

[24]  Mark Gerstein,et al.  Personal phenotypes to go with personal genomes , 2009, Molecular systems biology.

[25]  Adam A. Margolin,et al.  The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity , 2012, Nature.

[26]  Hanlee P. Ji,et al.  Corrigendum: Performance comparison of whole-genome sequencing platforms , 2012, Nature Biotechnology.

[27]  Irmtraud M. Meyer,et al.  The clonal and mutational evolution spectrum of primary triple-negative breast cancers , 2012, Nature.

[28]  A. Darzi,et al.  Gut microbiome-host interactions in health and disease , 2011, Genome Medicine.

[29]  L. Langman,et al.  The challenges of personalized medicine. , 2012, Clinical biochemistry.

[30]  Giovanni Parmigiani,et al.  The Predictive Capacity of Personal Genome Sequencing , 2012, Science Translational Medicine.

[31]  Kevin Y. Yip,et al.  Extensive In Vivo Metabolite-Protein Interactions Revealed by Large-Scale Systematic Analyses , 2010, Cell.

[32]  Aravinda Chakravarti,et al.  Genomics Is Not Enough , 2011, Science.

[33]  Huanming Yang,et al.  Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor , 2012, Cell.

[34]  Stephen L. Hauser,et al.  Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis , 2010, Nature.

[35]  David R. Murdock,et al.  Whole-Genome Sequencing for Optimized Patient Management , 2011, Science Translational Medicine.

[36]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[37]  Mark Gerstein,et al.  Personal genome sequencing: current approaches and challenges. , 2010, Genes & development.

[38]  E. Birney,et al.  A small cell lung cancer genome reports complex tobacco exposure signatures , 2009, Nature.

[39]  Linfeng Wu,et al.  Overcoming the dynamic range problem in mass spectrometry-based shotgun proteomics , 2006, Expert review of proteomics.

[40]  Mingyao Li,et al.  Widespread RNA and DNA Sequence Differences in the Human Transcriptome , 2011, Science.

[41]  Tom Misteli,et al.  RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E) , 2011, Nature.

[42]  Steven P Gygi,et al.  The SCX/IMAC enrichment approach for global phosphorylation analysis by mass spectrometry , 2008, Nature Protocols.

[43]  F. Mazzocchi.  Complexity and the reductionism–holism debate in systems biology , 2012, Wiley interdisciplinary reviews. Systems biology and medicine.

[44]  Euan A Ashley,et al.  A public resource facilitating clinical use of genomes , 2012, Proceedings of the National Academy of Sciences.

[45]  Muin J Khoury,et al.  A population approach to precision medicine. , 2012, American journal of preventive medicine.

[46]  Alexander A. Morgan,et al.  Clinical assessment incorporating a personal genome , 2010, The Lancet.

[47]  Jessica C. Ebert,et al.  Accurate whole genome sequencing and haplotyping from10-20 human cells , 2012, Nature.

[48]  A. Ashworth,et al.  A whole‐genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor‐negative and ‐positive breast cancers , 2012, The Journal of pathology.

[49]  L. Mucke,et al.  Alzheimer Mechanisms and Therapeutic Strategies , 2012, Cell.

[50]  P. D. Rijk,et al.  Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing , 2011, Nature Biotechnology.

[51]  S. Kaufman.  Correction for Kaufman, A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients , 1999, Proceedings of the National Academy of Sciences.

[52]  L. Hood,et al.  A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory. , 2012, New biotechnology.

[53]  Alexander A. Morgan,et al.  Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes , 2012, Proceedings of the National Academy of Sciences.

[54]  On beyond GWAS , 2010, Nature Genetics.

[55]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[56]  G. Omenn,et al.  Evolution of Translational Omics: Lessons Learned and the Path Forward , 2013 .

[57]  F. Real,et al.  An improved quantitative mass spectrometry analysis of tumor specific mutant proteins at high sensitivity , 2012, Proteomics.

[58]  David J. Elliott,et al.  Alternative splicing and biological heterogeneity in prostate cancer , 2009, Nature Reviews Urology.

[59]  Juliane C. Dohm,et al.  Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia , 2011, Nature.

[60]  L. Smarr.  Quantifying your body: a how-to guide from a systems biology perspective. , 2012, Biotechnology journal.

[61]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

[62]  P. Shannon,et al.  Analysis of Genetic Inheritance in a Family Quartet by Whole-Genome Sequencing , 2010, Science.

[63]  Hidenori Ojima,et al.  High-resolution characterization of a hepatocellular carcinoma genome , 2011, Nature Genetics.

[64]  N. Cho,et al.  In situ identification and localization of IGHA2 in the breast tumor microenvironment by mass spectrometry. , 2012, Journal of proteome research.

[65]  Russ B. Altman,et al.  Bioinformatics challenges for personalized medicine , 2011, Bioinform..

[66]  John R. Yates,et al.  The biological impact of mass-spectrometry-based proteomics , 2007, Nature.

[67]  Massimo Loda,et al.  Investigative pathology: leading the post-genomic revolution , 2012, Laboratory Investigation.

[68]  J. Nielsen,et al.  Nutritional systems biology: definitions and approaches. , 2009, Annual review of nutrition.

[69]  Tom Royce,et al.  A comprehensive catalogue of somatic mutations from a human cancer genome , 2010, Nature.

[70]  M. Gerstein,et al.  Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing , 2010, Proceedings of the National Academy of Sciences.

[71]  Neema Jamshidi,et al.  Individualized therapy of HHT driven by network analysis of metabolomic profiles , 2011, BMC Systems Biology.

[72]  Julian L. Griffin,et al.  Metabolic profiles of cancer cells , 2004, Nature Reviews Cancer.

[73]  N. Serkova,et al.  Metabolomics of cancer. , 2009, Methods in molecular biology.

[74]  Omar E. Cornejo,et al.  Phased Whole-Genome Genetic Risk in a Family Quartet Using a Major Allele Reference Sequence , 2011, PLoS genetics.

[75]  Dmitry Pushkarev,et al.  Single-molecule sequencing of an individual human genome , 2009, Nature Biotechnology.

[76]  Ara Darzi,et al.  Preparing for precision medicine. , 2012, The New England journal of medicine.

[77]  Joseph Loscalzo,et al.  Systems pharmacology, pharmacogenetics, and clinical trial design in network medicine , 2012, Wiley interdisciplinary reviews. Systems biology and medicine.

[78]  M. Dietel,et al.  Personalized cancer medicine and the future of pathology , 2011, Virchows Archiv.

[79]  Hugo Y. K. Lam,et al.  Performance comparison of exome DNA sequencing technologies , 2011, Nature Biotechnology.

[80]  James Taylor,et al.  Next-generation sequencing data interpretation: enhancing reproducibility and accessibility , 2012, Nature Reviews Genetics.

[81]  S. Brahmachari,et al.  Pharmacogenomics: a path to predictive medicine for schizophrenia. , 2006, Pharmacogenomics.

[82]  Trey Ideker,et al.  Boosting Signal-to-Noise in Complex Biology: Prior Knowledge Is Power , 2011, Cell.

[83]  Lee E. Edsall,et al.  Human DNA methylomes at base resolution show widespread epigenomic differences , 2009, Nature.

[84]  Hugo Y. K. Lam,et al.  Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes , 2012, Cell.

[85]  Li Ding,et al.  Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. , 2011, JAMA.

[86]  O. Delattre,et al.  Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer , 2008, Proceedings of the National Academy of Sciences.

[87]  Jared C. Roach,et al.  Chromosomal haplotypes by genetic phasing of human families. , 2011, American journal of human genetics.