{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T22:34:13Z","timestamp":1775514853528,"version":"3.50.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes for Environmental Health","award":["K23ES027221"],"award-info":[{"award-number":["K23ES027221"]}]},{"name":"Centers for Disease Control and Prevention\/Agency for Toxic Substances and Disease Registry","award":["200-2013-56856"],"award-info":[{"award-number":["200-2013-56856"]}]},{"name":"Katherine Rayner Fund"},{"name":"Program for Neurology Research and Discovery"},{"name":"Robert and Katherine Jacobs Environmental Health Initiative"},{"DOI":"10.13039\/100013013","name":"Target ALS Foundation","doi-asserted-by":"crossref","award":["N021258-00"],"award-info":[{"award-number":["N021258-00"]}],"id":[{"id":"10.13039\/100013013","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cariology Restorative Sciences and Endodontics Department Funds at University of Michigan School of Dentistry"},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K99HD087523"],"award-info":[{"award-number":["K99HD087523"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Environmental Health Sciences","doi-asserted-by":"crossref","award":["DP2ES025453, R01ES024674, U2CES026561, and P30ES023515"],"award-info":[{"award-number":["DP2ES025453, R01ES024674, U2CES026561, and P30ES023515"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Michigan A. Alfred Taubman Medical Research Institute"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1007773","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T17:24:26Z","timestamp":1586971466000},"page":"e1007773","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dysregulated biodynamics in metabolic attractor systems precede the emergence of amyotrophic lateral sclerosis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-3868","authenticated-orcid":true,"given":"Paul","family":"Curtin","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-0492","authenticated-orcid":true,"given":"Christine","family":"Austin","sequence":"additional","affiliation":[]},{"given":"Austen","family":"Curtin","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-5907","authenticated-orcid":true,"given":"Chris","family":"Gennings","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-4190","authenticated-orcid":true,"given":"Claudia","family":"Figueroa-Romero","sequence":"additional","affiliation":[]},{"given":"Kristen A.","family":"Mikhail","sequence":"additional","affiliation":[]},{"given":"Tatiana M.","family":"Botero","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-6637","authenticated-orcid":true,"given":"Stephen A.","family":"Goutman","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-2694","authenticated-orcid":true,"given":"Eva L.","family":"Feldman","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-4657","authenticated-orcid":true,"given":"Manish","family":"Arora","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"issue":"5","key":"pcbi.1007773.ref001","article-title":"A Signature of Attractor Dynamics in the CA3 Region of the Hippocampus. Plos Comput Biol","volume":"10","author":"C Renno-Costa","year":"2014"},{"issue":"6","key":"pcbi.1007773.ref002","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1162\/089976600300015385","article-title":"Attractor dynamics in feedforward neural networks","volume":"12","author":"LK Saul","year":"2000","journal-title":"Neural Comput"},{"issue":"5723","key":"pcbi.1007773.ref003","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1126\/science.1108905","article-title":"Attractor dynamics in the hippocampal representation of the local environment","volume":"308","author":"TJ Wills","year":"2005","journal-title":"Science"},{"issue":"1","key":"pcbi.1007773.ref004","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1530\/ror.0.0030013","article-title":"Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology","volume":"3","author":"J. Arendt","year":"1998","journal-title":"Rev Reprod"},{"issue":"3","key":"pcbi.1007773.ref005","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3201\/eid0703.017301","article-title":"Seasonal variation in host susceptibility and cycles of certain infectious diseases","volume":"7","author":"SF Dowell","year":"2001","journal-title":"Emerg Infect Dis"},{"issue":"17","key":"pcbi.1007773.ref006","doi-asserted-by":"crossref","first-page":"R784","DOI":"10.1016\/j.cub.2008.07.003","article-title":"Human responses to the geophysical daily, annual and lunar cycles","volume":"18","author":"RG Foster","year":"2008","journal-title":"Curr Biol"},{"issue":"8","key":"pcbi.1007773.ref007","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s11121-017-0803-3","article-title":"Dynamical Systems Modeling of Couple Interaction: a New Method for Assessing Intervention Impact Across the Transition to Parenthood","volume":"18","author":"ME Feinberg","year":"2017","journal-title":"Prev Sci"},{"issue":"2","key":"pcbi.1007773.ref008","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/MOP.0b013e32835e9084","article-title":"Teeth as a biomarker of past chemical exposure","volume":"25","author":"M Arora","year":"2013","journal-title":"Curr Opin Pediatr"},{"issue":"7","key":"pcbi.1007773.ref009","doi-asserted-by":"crossref","first-page":"e41010","DOI":"10.1371\/journal.pone.0041010","article-title":"Methods for detecting early warnings of critical transitions in time series illustrated using simulated ecological data","volume":"7","author":"V Dakos","year":"2012","journal-title":"PLoS One"},{"issue":"6053","key":"pcbi.1007773.ref010","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.1210657","article-title":"Global Resilience of Tropical Forest and Savanna to Critical Transitions","volume":"334","author":"M Hirota","year":"2011","journal-title":"Science"},{"key":"pcbi.1007773.ref011","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms5344","article-title":"Tipping elements in the human intestinal ecosystem","volume":"5","author":"L Lahti","year":"2014","journal-title":"Nat Commun"},{"issue":"1","key":"pcbi.1007773.ref012","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5194\/cp-6-77-2010","article-title":"Potential analysis reveals changing number of climate states during the last 60 kyr","volume":"6","author":"VN Livina","year":"2010","journal-title":"Clim Past"},{"issue":"11\u201312","key":"pcbi.1007773.ref013","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1007\/s00382-010-0980-2","article-title":"Changing climate states and stability: from Pliocene to present","volume":"37","author":"VN Livina","year":"2011","journal-title":"Clim Dynam"},{"issue":"4","key":"pcbi.1007773.ref014","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1890\/15-1047.1","article-title":"Balls, cups, and quasi-potentials: quantifying stability in stochastic systems","volume":"97","author":"BC Nolting","year":"2016","journal-title":"Ecology"},{"issue":"5","key":"pcbi.1007773.ref015","first-page":"1332","article-title":"Diagnosis and Clinical Management of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders","volume":"23","author":"SA Goutman","year":"2017","journal-title":"Continuum (Minneap Minn)"},{"issue":"1\u20132","key":"pcbi.1007773.ref016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000315405","article-title":"The association of exposure to lead, mercury, and selenium and the development of amyotrophic lateral sclerosis and the epigenetic implications","volume":"8","author":"B Callaghan","year":"2011","journal-title":"Neurodegener Dis"},{"issue":"7","key":"pcbi.1007773.ref017","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1001\/jamaneurol.2016.0594","article-title":"Association of Environmental Toxins With Amyotrophic Lateral Sclerosis","volume":"73","author":"FC Su","year":"2016","journal-title":"JAMA Neurol"},{"key":"pcbi.1007773.ref018","article-title":"High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis","author":"SA Goutman","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"pcbi.1007773.ref019","doi-asserted-by":"crossref","first-page":"e97805","DOI":"10.1371\/journal.pone.0097805","article-title":"Determining prenatal, early childhood and cumulative long-term lead exposure using micro-spatial deciduous dentine levels","volume":"9","author":"M Arora","year":"2014","journal-title":"PLoS One"},{"issue":"7453","key":"pcbi.1007773.ref020","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature12169","article-title":"Barium distributions in teeth reveal early-life dietary transitions in primates","volume":"498","author":"C Austin","year":"2013","journal-title":"Nature"},{"issue":"6053","key":"pcbi.1007773.ref021","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.1210657","article-title":"Global resilience of tropical forest and savanna to critical transitions","volume":"334","author":"M Hirota","year":"2011","journal-title":"Science"},{"issue":"5","key":"pcbi.1007773.ref022","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/ng.3811","article-title":"Potential energy landscapes identify the information-theoretic nature of the epigenome","volume":"49","author":"G Jenkinson","year":"2017","journal-title":"Nature genetics"},{"key":"pcbi.1007773.ref023","doi-asserted-by":"crossref","first-page":"4344","DOI":"10.1038\/ncomms5344","article-title":"Tipping elements in the human intestinal ecosystem","volume":"5","author":"L Lahti","year":"2014","journal-title":"Nat Commun"},{"key":"pcbi.1007773.ref024","first-page":"345","article-title":"Reconstruction Theory and Nonlinear Time Series Analysis","volume":"3","author":"F. Takens","year":"2010","journal-title":"Handbook of Dynamical Systems"},{"issue":"4","key":"pcbi.1007773.ref025","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1074\/jbc.M110.186999","article-title":"Copper and zinc metallation status of copper-zinc superoxide dismutase from amyotrophic lateral sclerosis transgenic mice","volume":"286","author":"HL Lelie","year":"2011","journal-title":"J Biol Chem"},{"key":"pcbi.1007773.ref026","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.freeradbiomed.2016.04.028","article-title":"Iron-sulfur cluster damage by the superoxide radical in neural tissues of the SOD1(G93A) ALS rat model","volume":"96","author":"A Popovic-Bijelic","year":"2016","journal-title":"Free Radic Biol Med"},{"issue":"11","key":"pcbi.1007773.ref027","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrneurol.2013.203","article-title":"The epidemiology of ALS: a conspiracy of genes, environment and time","volume":"9","author":"A Al-Chalabi","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"pcbi.1007773.ref028","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40035-017-0087-3","article-title":"Environmental insults: critical triggers for amyotrophic lateral sclerosis","volume":"6","author":"B Yu","year":"2017","journal-title":"Transl Neurodegener"},{"issue":"5","key":"pcbi.1007773.ref029","doi-asserted-by":"crossref","first-page":"eaat1293","DOI":"10.1126\/sciadv.aat1293","article-title":"Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder","volume":"4","author":"P Curtin","year":"2018","journal-title":"Sci Adv"},{"key":"pcbi.1007773.ref030","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1017\/erm.2017.9","article-title":"Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis","volume":"19","author":"FJ Gil-Bea","year":"2017","journal-title":"Expert Rev Mol Med"},{"key":"pcbi.1007773.ref031","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3389\/fnins.2018.00933","article-title":"Systems Biology Understanding of the Effects of Lithium on Affective and Neurodegenerative Disorders","volume":"12","author":"W Ge","year":"2018","journal-title":"Front Neurosci"},{"issue":"3","key":"pcbi.1007773.ref032","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/mp.2016.96","article-title":"Lithium suppression of tau induces brain iron accumulation and neurodegeneration","volume":"22","author":"P Lei","year":"2017","journal-title":"Mol Psychiatry"},{"key":"pcbi.1007773.ref033","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.envres.2017.07.048","article-title":"Metals and neurodegenerative diseases. A systematic review","volume":"159","author":"CE Cicero","year":"2017","journal-title":"Environmental research"},{"key":"pcbi.1007773.ref034","doi-asserted-by":"crossref","first-page":"371","DOI":"10.12688\/f1000research.10476.1","article-title":"What causes amyotrophic lateral sclerosis?","volume":"6","author":"S Martin","year":"2017","journal-title":"F1000Res"},{"key":"pcbi.1007773.ref035","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/B978-0-444-64076-5.00039-9","article-title":"Emerging understanding of the genotype-phenotype relationship in amyotrophic lateral sclerosis","volume":"148","author":"SA Goutman","year":"2018","journal-title":"Handb Clin Neurol"},{"issue":"9","key":"pcbi.1007773.ref036","doi-asserted-by":"crossref","DOI":"10.3390\/molecules22091429","article-title":"The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase","volume":"22","author":"I Sirangelo","year":"2017","journal-title":"Molecules"},{"issue":"5","key":"pcbi.1007773.ref037","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis","volume":"1","author":"World Federation of Neurology Research Group on Motor Neuron D","year":"2000","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"issue":"3","key":"pcbi.1007773.ref038","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.nbd.2007.07.022","article-title":"Mouse models of diabetic neuropathy","volume":"28","author":"KA Sullivan","year":"2007","journal-title":"Neurobiol Dis"},{"issue":"9","key":"pcbi.1007773.ref039","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1021\/es203569f","article-title":"Determining fetal manganese exposure from mantle dentine of deciduous teeth","volume":"46","author":"M Arora","year":"2012","journal-title":"Environ Sci Technol"},{"issue":"5","key":"pcbi.1007773.ref040","article-title":"Tooth lead levels as an estimate of lead body burden in rats following pre- and neonatal exposure","author":"M Arora","year":"2015","journal-title":"RSC Advances"},{"key":"pcbi.1007773.ref041","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.envres.2017.03.004","article-title":"Tooth manganese as a biomarker of exposure and body burden in rats","volume":"155","author":"C Austin","year":"2017","journal-title":"Environmental research"},{"issue":"2","key":"pcbi.1007773.ref042","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/MOP.0000000000000327","article-title":"The tooth exposome in children's health research","volume":"28","author":"SS Andra","year":"2016","journal-title":"Curr Opin Pediatr"},{"key":"pcbi.1007773.ref043","doi-asserted-by":"crossref","first-page":"15493","DOI":"10.1038\/ncomms15493","article-title":"Fetal and postnatal metal dysregulation in autism","volume":"8","author":"M Arora","year":"2017","journal-title":"Nat Commun"},{"key":"pcbi.1007773.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eurpsy.2016.03.006","article-title":"Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers","volume":"36","author":"A Modabbernia","year":"2016","journal-title":"Eur Psychiatry"},{"key":"pcbi.1007773.ref045","volume-title":"Wheeler's Dental Anatomy, Physiology and Occlusion","author":"M Ash","year":"2002"},{"issue":"5\u20136","key":"pcbi.1007773.ref046","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0375-9601(02)01170-2","article-title":"Nonlinear analysis of bivariate data with cross recurrence plots","volume":"302","author":"N Marwan","year":"2002","journal-title":"Phys Lett A"},{"issue":"5\u20136","key":"pcbi.1007773.ref047","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.physrep.2006.11.001","article-title":"Recurrence plots for the analysis of complex systems","volume":"438","author":"N Marwan","year":"2007","journal-title":"Phys Rep"},{"issue":"11","key":"pcbi.1007773.ref048","doi-asserted-by":"crossref","first-page":"e0187049","DOI":"10.1371\/journal.pone.0187049","article-title":"Recurrence quantification analysis to characterize cyclical components of environmental elemental exposures during fetal and postnatal development","volume":"12","author":"P Curtin","year":"2017","journal-title":"PLoS One"},{"issue":"41","key":"pcbi.1007773.ref049","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1016\/j.physleta.2009.08.052","article-title":"Simpler methods do it better: Success of Recurrence Quantification Analysis as a general purpose data analysis tool","volume":"373","author":"CL Webber","year":"2009","journal-title":"Phys Lett A"},{"issue":"2","key":"pcbi.1007773.ref050","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/jappl.1994.76.2.965","article-title":"Dynamical Assessment of Physiological Systems and States Using Recurrence Plot Strategies","volume":"76","author":"CL Webber","year":"1994","journal-title":"J Appl Physiol"},{"issue":"1","key":"pcbi.1007773.ref051","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41398-019-0567-6","article-title":"Dynamical properties of elemental metabolism distinguish attention deficit hyperactivity disorder from autism spectrum disorder","volume":"9","author":"C Austin","year":"2019","journal-title":"Transl Psychiatry"},{"key":"pcbi.1007773.ref052","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/9781118575574","volume-title":"Multivariate Density Estimation: Theory, Practice, and Visualization","author":"DW Scott","year":"2015"},{"key":"pcbi.1007773.ref053","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1145\/2939672.2939785","article-title":"XGBoost: A Scalable Tree Boosting System","author":"TQ Chen","year":"2016","journal-title":"Kdd'16: Proceedings of the 22nd Acm Sigkdd International Conference on Knowledge Discovery and Data Mining"},{"issue":"2","key":"pcbi.1007773.ref054","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1214\/aos\/1016218223","article-title":"Additive logistic regression: A statistical view of boosting\u2014Rejoinder","volume":"28","author":"J Friedman","year":"2000","journal-title":"Ann Stat"},{"issue":"5","key":"pcbi.1007773.ref055","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1214\/aos\/1013203450","article-title":"Greedy function approximation: A gradient boosting machine","volume":"29","author":"JH Friedman","year":"2001","journal-title":"Ann Stat"},{"issue":"584","key":"pcbi.1007773.ref056","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1256\/003590002320603584","article-title":"Areas beneath the relative operating characteristics (ROC) and relative operating levels (ROL) curves: Statistical significance and interpretation","volume":"128","author":"SJ Mason","year":"2002","journal-title":"Q J Roy Meteor Soc"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T11:04:02Z","timestamp":1666350242000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1007773"}},"subtitle":[],"editor":[{"given":"Pedro","family":"Mendes","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1007773","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]}}}