Networks of neuroinjury semantic predications to identify biomarkers for mild traumatic brain injury

ObjectiveMild traumatic brain injury (mTBI) has high prevalence in the military, among athletes, and in the general population worldwide (largely due to falls). Consequences can include a range of neuropsychological disorders. Unfortunately, such neural injury often goes undiagnosed due to the difficulty in identifying symptoms, so the discovery of an effective biomarker would greatly assist diagnosis; however, no single biomarker has been identified. We identify several body substances as potential components of a panel of biomarkers to support the diagnosis of mild traumatic brain injury.MethodsOur approach to diagnostic biomarker discovery combines ideas and techniques from systems medicine, natural language processing, and graph theory. We create a molecular interaction network that represents neural injury and is composed of relationships automatically extracted from the literature. We retrieve citations related to neurological injury and extract relationships (semantic predications) that contain potential biomarkers. After linking all relationships together to create a network representing neural injury, we filter the network by relationship frequency and concept connectivity to reduce the set to a manageable size of higher interest substances.Results99,437 relevant citations yielded 26,441 unique relations. 18,085 of these contained a potential biomarker as subject or object with a total of 6246 unique concepts. After filtering by graph metrics, the set was reduced to 1021 relationships with 49 unique concepts, including 17 potential biomarkers.ConclusionWe created a network of relationships containing substances derived from 99,437 citations and filtered using graph metrics to provide a set of 17 potential biomarkers. We discuss the interaction of several of these (glutamate, glucose, and lactate) as the basis for more effective diagnosis than is currently possible. This method provides an opportunity to focus the effort of wet bench research on those substances with the highest potential as biomarkers for mTBI.

[1]  Christopher S. Ogilvy,et al.  Predictive markers in traumatic brain injury: opportunities for a serum biosignature , 2014, British journal of neurosurgery.

[2]  J. Borg,et al.  Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. , 2004, Journal of rehabilitation medicine.

[3]  Marcelo Fiszman,et al.  Semantic MEDLINE for Discovery Browsing: Using Semantic Predications and the Literature-Based Discovery Paradigm to Elucidate a Mechanism for the Obesity Paradox , 2013, AMIA.

[4]  H. Bramlett,et al.  The potential utility of blood-derived biochemical markers as indicators of early clinical trends following severe traumatic brain injury. , 2014, World neurosurgery.

[5]  Inyoul Lee,et al.  Systems Biology and the Discovery of Diagnostic Biomarkers , 2010, Disease markers.

[6]  Guilherme Del Fiol,et al.  Automatically Extracting Sentences from Medline Citations to Support Clinicians' Information Needs , 2012, 2012 IEEE Second International Conference on Healthcare Informatics, Imaging and Systems Biology.

[7]  H. V. Jagadish,et al.  Literature-based discovery of diabetes- and ROS-related targets , 2010, BMC Medical Genomics.

[8]  Stephen W Marshall,et al.  Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. , 2003, JAMA.

[9]  T. Rindflesch,et al.  A closed literature-based discovery technique finds a mechanistic link between hypogonadism and diminished sleep quality in aging men. , 2012, Sleep.

[10]  Joyce A. Mitchell,et al.  Using literature-based discovery to identify disease candidate genes , 2005, Int. J. Medical Informatics.

[11]  Lucila Ohno-Machado,et al.  Natural language processing: an introduction , 2011, J. Am. Medical Informatics Assoc..

[12]  Yongqun He,et al.  Identification of fever and vaccine-associated gene interaction networks using ontology-based literature mining , 2012, Journal of Biomedical Semantics.

[13]  Barend Mons,et al.  Generic Information Can Retrieve Known Biological Associations: Implications for Biomedical Knowledge Discovery , 2013, PloS one.

[14]  J F Stover,et al.  Glutamate and taurine are increased in ventricular cerebrospinal fluid of severely brain-injured patients. , 1999, Journal of neurotrauma.

[15]  Ying He,et al.  Biological Entity Recognition with Conditional Random Fields , 2008, AMIA.

[16]  Thomas C. Rindflesch,et al.  Predicting High-Throughput Screening Results With Scalable Literature-Based Discovery Methods , 2014, CPT: pharmacometrics & systems pharmacology.

[17]  Jeffrey V Rosenfeld,et al.  Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Hua Xu,et al.  Identifying Plausible Adverse Drug Reactions Using Knowledge Extracted from the Literature , 2014, AMIA.

[19]  D L McArthur,et al.  Metabolic Crisis After Traumatic Brain Injury is Associated with a Novel Microdialysis Proteome , 2010, Neurocritical care.

[20]  Nicola Biasca,et al.  Minor traumatic brain injury in sports: a review in order to prevent neurological sequelae. , 2007, Progress in brain research.

[21]  P. Dash,et al.  Biomarkers for the diagnosis and prognosis of mild traumatic brain injury/concussion. , 2013, Journal of neurotrauma.

[22]  Gang Wang,et al.  New insight into genes in association with asthma: literature‐based mining and network centrality analysis , 2013, Chinese medical journal.

[23]  Amit P. Sheth,et al.  A graph-based recovery and decomposition of Swanson's hypothesis using semantic predications , 2013, J. Biomed. Informatics.

[24]  Eileen Maloney,et al.  A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. , 2009, Journal of neurotrauma.

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

[26]  Erik M. van Mulligen,et al.  Finding potentially new multimorbidity patterns of psychiatric and somatic diseases: exploring the use of literature-based discovery in primary care research , 2014, J. Am. Medical Informatics Assoc..

[27]  Vassilis Virvilis,et al.  Literature mining, ontologies and information visualization for drug repurposing , 2011, Briefings Bioinform..

[28]  Marcelo Fiszman,et al.  The interaction of domain knowledge and linguistic structure in natural language processing: interpreting hypernymic propositions in biomedical text , 2003, J. Biomed. Informatics.

[29]  John D Corrigan,et al.  Long-term consequences of traumatic brain injury. , 2009, The Journal of head trauma rehabilitation.

[30]  Borut Peterlin,et al.  Semantic Relations for Interpreting DNA Microarray Data , 2009, AMIA.

[31]  Dongwook Shin,et al.  Using semantic predications to characterize the clinical cardiovascular literature. , 2008, AMIA ... Annual Symposium proceedings. AMIA Symposium.

[32]  Halil Kilicoglu,et al.  Augmenting Microarray Data with Literature-Based Knowledge to Enhance Gene Regulatory Network Inference , 2014, PLoS Comput. Biol..

[33]  T. Lo,et al.  Pediatric brain trauma outcome prediction using paired serum levels of inflammatory mediators and brain-specific proteins. , 2009, Journal of neurotrauma.

[34]  J. Langlois,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths , 2006 .

[35]  Dongwook Shin,et al.  Degree centrality for semantic abstraction summarization of therapeutic studies , 2011, J. Biomed. Informatics.

[36]  David J Petron,et al.  Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. , 2014, Clinical biochemistry.

[37]  B. Jordan,et al.  Chronic Traumatic Brain Injury Associated with Boxing , 2000, Seminars in neurology.

[38]  Thomas C. Rindflesch,et al.  Synonym, Topic Model and Predicate-Based Query Expansion for Retrieving Clinical Documents , 2012, AMIA.

[39]  Dietrich Rebholz-Schuhmann,et al.  PCorral—interactive mining of protein interactions from MEDLINE , 2013, Database J. Biol. Databases Curation.

[40]  Alan R. Aronson,et al.  An overview of MetaMap: historical perspective and recent advances , 2010, J. Am. Medical Informatics Assoc..

[41]  M. Kraut,et al.  Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. , 2013, JAMA neurology.

[42]  R. Bullock,et al.  Biomarkers for the Clinical Differential Diagnosis in Traumatic Brain Injury—A Systematic Review , 2013, CNS neuroscience & therapeutics.

[43]  Peter Davies,et al.  Discovering discovery patterns with predication-based Semantic Indexing , 2012, J. Biomed. Informatics.

[44]  Halil Kilicoglu,et al.  Using semantic predications to uncover drug-drug interactions in clinical data , 2014, J. Biomed. Informatics.

[45]  Thomas Paparrigopoulos,et al.  Melatonin secretion after head injury: A pilot study , 2006, Brain injury.

[46]  Shyam Visweswaran,et al.  Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids , 2014, Journal of Clinical Bioinformatics.

[47]  Trevor Cohen,et al.  Predication-based Semantic Indexing: Permutations as a Means to Encode Predications in Semantic Space , 2009, AMIA.

[48]  A. Baker,et al.  Application of Blood-Based Biomarkers in Human Mild Traumatic Brain Injury , 2013, Front. Neurol..

[49]  Olivier Bodenreider,et al.  The Unified Medical Language System (UMLS): integrating biomedical terminology , 2004, Nucleic Acids Res..

[50]  Xiang Zhang,et al.  Ontology summarization based on rdf sentence graph , 2007, WWW '07.

[51]  Dimitar Hristovski,et al.  A Fast Document Classification Algorithm for Gene Symbol Disambiguation in the BITOLA Literature-Based Discovery Support System , 2008, AMIA.

[52]  Dragomir R. Radev,et al.  Literature-Based Discovery of IFN-γ and Vaccine-Mediated Gene Interaction Networks , 2010, Journal of biomedicine & biotechnology.

[53]  Barend Mons,et al.  Online tools to support literature-based discovery in the life sciences , 2005, Briefings Bioinform..

[54]  Josef Ling,et al.  Neurometabolite concentrations in gray and white matter in mild traumatic brain injury: an 1H-magnetic resonance spectroscopy study. , 2009, Journal of neurotrauma.

[55]  Hongfei Lin,et al.  Enhancing Biomedical Text Summarization Using Semantic Relation Extraction , 2011, PloS one.

[56]  Carlo A. Trugenberger,et al.  Discovery of novel biomarkers and phenotypes by semantic technologies , 2012, BMC Bioinformatics.

[57]  Borut Peterlin,et al.  Using literature-based discovery to identify novel therapeutic approaches. , 2013, Cardiovascular & hematological agents in medicinal chemistry.

[58]  Garnette R Sutherland,et al.  The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. , 2009, Brain : a journal of neurology.

[59]  M. Wald,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006 , 2010 .

[60]  Charles Gasparovic,et al.  A longitudinal proton magnetic resonance spectroscopy study of mild traumatic brain injury. , 2011, Journal of neurotrauma.

[61]  M. Helfaer,et al.  Alterations in Ionized and Total Blood Magnesium After Experimental Traumatic Brain Injury , 1999, Journal of neurochemistry.

[62]  Martin Halvey,et al.  WWW '07: Proceedings of the 16th international conference on World Wide Web , 2007, WWW 2007.

[63]  Trevor Cohen,et al.  Discovery by scent: Discovery browsing system based on the Information Foraging Theory , 2012, 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops.

[64]  Carol Friedman,et al.  Exploiting Semantic Relations for Literature-Based Discovery , 2006, AMIA.

[65]  David C Viano,et al.  Concussion in professional football: summary of the research conducted by the National Football League's Committee on Mild Traumatic Brain Injury. , 2006, Neurosurgical focus.

[66]  Carol Friedman,et al.  Towards automatic extraction of research findings from the literature. , 2007, AMIA ... Annual Symposium proceedings. AMIA Symposium.

[67]  Michael A. Kiraly,et al.  Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion) are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia , 2007, TheScientificWorldJournal.

[68]  Bruce E. Bray,et al.  Semantic Processing to Support Clinical Guideline Development , 2008, AMIA.

[69]  Halil Kilicoglu,et al.  Using the Literature-Based Discovery Paradigm to Investigate Drug Mechanisms , 2007, AMIA.

[70]  Halil Kilicoglu,et al.  SemMedDB: a PubMed-scale repository of biomedical semantic predications , 2012, Bioinform..

[71]  M. Levy,et al.  Concussions in soccer: a current understanding. , 2012, World neurosurgery.

[72]  Colman B Taylor,et al.  Incidence, Risk, and Protective Factors of Mild Traumatic Brain Injury in a Cohort of Australian Nonprofessional Male Rugby Players , 2009, The American journal of sports medicine.

[73]  Riccardo Bellazzi,et al.  A Unified Medical Language System (UMLS) Based System for Literature-Based Discovery in Medicine , 2013, MedInfo.

[74]  S. Timmons,et al.  An update on traumatic brain injuries. , 2012, Journal of neurosurgical sciences.

[75]  Borut Peterlin,et al.  Integration of Data from Omic Studies with the Literature-Based Discovery towards Identification of Novel Treatments for Neovascularization in Diabetic Retinopathy , 2013, BioMed research international.

[76]  Yi Hu,et al.  Simulation of Swanson's Literature-Based Discovery: Anandamide Treatment Inhibits Growth of Gastric Cancer Cells In Vitro and In Silico , 2014, PloS one.

[77]  Ying Liu,et al.  Using SemRep to Label Semantic Relations Extracted from Clinical Text , 2012, AMIA.