Systems and precision medicine approaches to diabetes heterogeneity: a Big Data perspective

Big Data, and in particular Electronic Health Records, provide the medical community with a great opportunity to analyze multiple pathological conditions at an unprecedented depth for many complex diseases, including diabetes. How can we infer on diabetes from large heterogeneous datasets? A possible solution is provided by invoking next-generation computational methods and data analytics tools within systems medicine approaches. By deciphering the multi-faceted complexity of biological systems, the potential of emerging diagnostic tools and therapeutic functions can be ultimately revealed. In diabetes, a multidimensional approach to data analysis is needed to better understand the disease conditions, trajectories and the associated comorbidities. Elucidation of multidimensionality comes from the analysis of factors such as disease phenotypes, marker types, and biological motifs while seeking to make use of multiple levels of information including genetics, omics, clinical data, and environmental and lifestyle factors. Examining the synergy between multiple dimensions represents a challenge. In such regard, the role of Big Data fuels the rise of Precision Medicine by allowing an increasing number of descriptions to be captured from individuals. Thus, data curations and analyses should be designed to deliver highly accurate predicted risk profiles and treatment recommendations. It is important to establish linkages between systems and precision medicine in order to translate their principles into clinical practice. Equivalently, to realize their full potential, the involved multiple dimensions must be able to process information ensuring inter-exchange, reducing ambiguities and redundancies, and ultimately improving health care solutions by introducing clinical decision support systems focused on reclassified phenotypes (or digital biomarkers) and community-driven patient stratifications.

[1]  Eve A Kerr,et al.  The impact of comorbid chronic conditions on diabetes care. , 2006, Diabetes care.

[2]  Danny Petrasek Systems Biology: The Case for a Systems Science Approach to Diabetes , 2008, Journal of diabetes science and technology.

[3]  D. Leroith,et al.  Type 2 diabetes and cancer: what is the connection? , 2010, The Mount Sinai journal of medicine, New York.

[4]  Edward Giovannucci,et al.  Diabetes and Cancer , 2010, Diabetes Care.

[5]  S. Suh,et al.  Diabetes and Cancer: Is Diabetes Causally Related to Cancer? , 2011, Diabetes & metabolism journal.

[6]  Thomas A. Down,et al.  Identification of Type 1 Diabetes–Associated DNA Methylation Variable Positions That Precede Disease Diagnosis , 2010, PLoS genetics.

[7]  G. Bianconi,et al.  Differential network entropy reveals cancer system hallmarks , 2012, Scientific Reports.

[8]  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.

[9]  Michael T. McManus,et al.  Research resource: RNA-Seq reveals unique features of the pancreatic β-cell transcriptome. , 2012, Molecular endocrinology.

[10]  M. McCarthy,et al.  Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. , 2012, Cell metabolism.

[11]  D. Madigan,et al.  Evaluating the impact of database heterogeneity on observational study results. , 2013, American journal of epidemiology.

[12]  Shelley A. Rusincovitch,et al.  A comparison of phenotype definitions for diabetes mellitus. , 2013, Journal of the American Medical Informatics Association : JAMIA.

[13]  David R. Kelley,et al.  Long noncoding RNAs regulate adipogenesis , 2013, Proceedings of the National Academy of Sciences.

[14]  Pietro Lio',et al.  Comorbidity: a multidimensional approach. , 2013, Trends in molecular medicine.

[15]  Tiinamaija Tuomi,et al.  The many faces of diabetes: a disease with increasing heterogeneity , 2014, The Lancet.

[16]  N. Rishe,et al.  Introduction to Personalized Medicine in Diabetes Mellitus , 2014, Rambam Maimonides medical journal.

[17]  Claudio Rigatto,et al.  Earlier Onset of Complications in Youth With Type 2 Diabetes , 2014, Diabetes Care.

[18]  Tudor I. Oprea,et al.  Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients , 2014, Nature Communications.

[19]  E. Bass,et al.  The Pharmacogenetics of Type 2 Diabetes: A Systematic Review , 2014, Diabetes Care.

[20]  David A. Sontag,et al.  Population-Level Prediction of Type 2 Diabetes From Claims Data and Analysis of Risk Factors , 2015, Big Data.

[21]  R. Hu,et al.  Cancer risk among patients with type 2 diabetes mellitus: a population-based prospective study in China , 2015, Scientific Reports.

[22]  Benjamin S. Glicksberg,et al.  Identification of type 2 diabetes subgroups through topological analysis of patient similarity , 2015, Science Translational Medicine.

[23]  M. Danova,et al.  Diabetes and cancer: A critical appraisal of the pathogenetic and therapeutic links. , 2015, Biomedical reports.

[24]  E. Capobianco Cancer hallmarks through the network lens , 2015 .

[25]  E. Karnieli,et al.  Personalized epigenetic management of diabetes. , 2015, Personalized medicine.

[26]  J. Florez Precision Medicine in Diabetes: Is It Time? , 2016, Diabetes Care.

[27]  E. Gakidou,et al.  Identifying High-Risk Neighborhoods Using Electronic Medical Records: A Population-Based Approach for Targeting Diabetes Prevention and Treatment Interventions , 2016, PloS one.

[28]  Tong Li,et al.  Electronic health record phenotyping improves detection and screening of type 2 diabetes in the general United States population: A cross-sectional, unselected, retrospective study , 2015, J. Biomed. Informatics.

[29]  Pedro J. Caraballo,et al.  Type 2 Diabetes Mellitus Trajectories and Associated Risks , 2016, Big Data.

[30]  Jianying Hu,et al.  Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study , 2016, Big Data.

[31]  D. Serraino,et al.  Cancer among patients with type 2 diabetes mellitus: A population-based cohort study in northeastern Italy. , 2016, Cancer epidemiology.

[32]  S. Wild,et al.  Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals , 2016, Diabetologia.

[33]  Søren Brunak,et al.  Diagnosis trajectories of prior multi-morbidity predict sepsis mortality , 2016, Scientific Reports.

[34]  D. Arnett,et al.  Precision Medicine, Genomics, and Public Health , 2016, Diabetes Care.

[35]  M. Dodson,et al.  Long noncoding RNAs in regulating adipogenesis: new RNAs shed lights on obesity , 2016, Cellular and Molecular Life Sciences.

[36]  S. Rich,et al.  The Impact of Precision Medicine in Diabetes: A Multidimensional Perspective , 2016, Diabetes Care.

[37]  E. Karnieli,et al.  Challenges of implementing personalized (precision) medicine: a focus on diabetes. , 2016, Personalized medicine.

[38]  B. Psaty,et al.  The Application of Genomics in Diabetes: Barriers to Discovery and Implementation , 2016, Diabetes Care.

[39]  Inigo Martincorena,et al.  Precision oncology for acute myeloid leukemia using a knowledge bank approach , 2017, Nature Genetics.

[40]  Christine Maric-Bilkan Sex differences in micro- and macro-vascular complications of diabetes mellitus. , 2017, Clinical science.

[41]  J. Tyner Integrating functional genomics to accelerate mechanistic personalized medicine , 2017, Cold Spring Harbor molecular case studies.

[42]  Eugenia R. McPeek Hinz,et al.  Assessing electronic health record phenotypes against gold-standard diagnostic criteria for diabetes mellitus , 2017, J. Am. Medical Informatics Assoc..

[43]  Andrew V Biankin,et al.  The road to precision oncology , 2017, Nature Genetics.