Multi-modal deep learning from imaging genomic data for schizophrenia classification.

Ayush Kanyal, Badhan Mazumder, Vince D Calhoun, Adrian Preda, Jessica Turner, Judith Ford, Dong Hye Ye
Author Information
  1. Ayush Kanyal: Department of Computer Science, Georgia State University, Atlanta, GA, United States.
  2. Badhan Mazumder: Department of Computer Science, Georgia State University, Atlanta, GA, United States.
  3. Vince D Calhoun: Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Atlanta, GA, United States.
  4. Adrian Preda: Department of Psychiatry and Human Behavior, Univeristy of California Irvine, Irvine, CA, United States.
  5. Jessica Turner: Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, United States.
  6. Judith Ford: Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States.
  7. Dong Hye Ye: Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Atlanta, GA, United States.

Abstract

Background: Schizophrenia (SZ) is a psychiatric condition that adversely affects an individual's cognitive, emotional, and behavioral aspects. The etiology of SZ, although extensively studied, remains unclear, as multiple factors come together to contribute toward its development. There is a consistent body of evidence documenting the presence of structural and functional deviations in the brains of individuals with SZ. Moreover, the hereditary aspect of SZ is supported by the significant involvement of genomics markers. Therefore, the need to investigate SZ from a multi-modal perspective and develop approaches for improved detection arises.
Methods: Our proposed method employed a deep learning framework combining features from structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and genetic markers such as single nucleotide polymorphism (SNP). For sMRI, we used a pre-trained DenseNet to extract the morphological features. To identify the most relevant functional connections in fMRI and SNPs linked to SZ, we applied a 1-dimensional convolutional neural network (CNN) followed by layerwise relevance propagation (LRP). Finally, we concatenated these obtained features across modalities and fed them to the extreme gradient boosting (XGBoost) tree-based classifier to classify SZ from healthy control (HC).
Results: Experimental evaluation on clinical dataset demonstrated that, compared to the outcomes obtained from each modality individually, our proposed multi-modal approach performed classification of SZ individuals from HC with an improved accuracy of 79.01%.
Conclusion: We proposed a deep learning based framework that selects multi-modal (sMRI, fMRI and genetic) features efficiently and fuse them to obtain improved classification scores. Additionally, by using Explainable AI (XAI), we were able to pinpoint and validate significant functional network connections and SNPs that contributed the most toward SZ classification, providing necessary interpretation behind our findings.

Keywords

References

  1. Schizophr Res. 2011 Dec;133(1-3):165-71 [PMID: 21996267]
  2. Neuron. 2014 Oct 22;84(2):262-74 [PMID: 25374354]
  3. BMC Neurosci. 2022 Jan 17;23(1):5 [PMID: 35038994]
  4. Curr Top Med Chem. 2012;12(21):2404-14 [PMID: 23279179]
  5. Eur Psychiatry. 2021 Dec 23;65(1):e1 [PMID: 34937587]
  6. Sensors (Basel). 2023 Jan 05;23(2): [PMID: 36679430]
  7. Molecules. 2010 Jul 12;15(7):4875-89 [PMID: 20657396]
  8. Schizophr Bull. 2016 May;42(3):538-41 [PMID: 26994396]
  9. Nat Biotechnol. 2006 Dec;24(12):1565-7 [PMID: 17160063]
  10. Front Hum Neurosci. 2021 Sep 09;15:720239 [PMID: 34566604]
  11. Comput Biol Med. 2022 Jul;146:105554 [PMID: 35569333]
  12. Comput Math Methods Med. 2021 Nov 9;2021:8437260 [PMID: 34795793]
  13. J Pers Med. 2020 Sep 15;10(3): [PMID: 32942564]
  14. IEEE J Biomed Health Inform. 2020 May;24(5):1333-1343 [PMID: 31536026]
  15. Med Image Anal. 2022 Jul;79:102470 [PMID: 35576821]
  16. Genome Biol. 2016 Aug 30;17(1):176 [PMID: 27572077]
  17. Annu Rev Biomed Eng. 2007;9:289-320 [PMID: 17391067]
  18. Nat Mach Intell. 2019 May;1(5):206-215 [PMID: 35603010]
  19. Neuroimage. 2013 Dec;83:384-96 [PMID: 23727316]
  20. Front Aging Neurosci. 2019 Jul 31;11:194 [PMID: 31417397]
  21. Tidsskr Nor Laegeforen. 2013 Apr 23;133(8):850-3 [PMID: 23612107]
  22. Stroke. 2018 Apr;49(4):912-918 [PMID: 29540608]
  23. Neuroimage. 2014 Jan 1;84:299-306 [PMID: 24004694]
  24. Schizophr Bull. 1987;13(1):9-22 [PMID: 3496659]
  25. Nature. 2014 Jul 24;511(7510):421-7 [PMID: 25056061]
  26. Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:3267-3272 [PMID: 34891938]
  27. Brain Res Brain Res Rev. 2000 Mar;31(2-3):357-63 [PMID: 10719163]
  28. JAMA Psychiatry. 2015 May;72(5):446-55 [PMID: 25786193]
  29. Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:3387-3390 [PMID: 34891966]
  30. J Neural Eng. 2023 Sep 28;20(5): [PMID: 37673060]
  31. Neuroimage. 2016 Jan 1;124(Pt B):1074-1079 [PMID: 26364863]
  32. Schizophr Bull. 2008 Mar;34(2):330-40 [PMID: 18227083]
  33. Schizophr Res. 2020 Mar;217:4-12 [PMID: 31780348]
  34. Psychiatr Genet. 2020 Feb;30(1):1-9 [PMID: 31764709]
  35. Am J Hum Genet. 2007 Sep;81(3):559-75 [PMID: 17701901]
  36. Schizophr Bull. 2014 Mar;40 Suppl 2:S131-7 [PMID: 24562492]
  37. BMC Med Imaging. 2022 Apr 13;22(1):69 [PMID: 35418051]
  38. Schizophr Res. 2020 Apr;218:107-115 [PMID: 32037204]
  39. Mol Psychiatry. 2020 Nov;25(11):2773-2785 [PMID: 32066828]
  40. Schizophr Res. 2022 May;243:330-341 [PMID: 34210562]
  41. J Med Genet. 2004 May;41(5):e63 [PMID: 15121791]
  42. Br J Psychiatry. 1995 Sep;167(3):343-9 [PMID: 7496643]

Word Cloud

Created with Highcharts 10.0.0SZfunctionalimagingmulti-modaldeeplearningfeaturessMRIclassificationstructuralimprovedproposedmagneticresonancefMRInetworktowardindividualssignificantmarkersframeworkgeneticsinglenucleotidepolymorphismSNPconnectionsSNPsobtainedHCXAIschizophreniaBackground:Schizophreniapsychiatricconditionadverselyaffectsindividual'scognitiveemotionalbehavioralaspectsetiologyalthoughextensivelystudiedremainsunclearmultiplefactorscometogethercontributedevelopmentconsistentbodyevidencedocumentingpresencedeviationsbrainsMoreoverhereditaryaspectsupportedinvolvementgenomicsThereforeneedinvestigateperspectivedevelopapproachesdetectionarisesMethods:methodemployedcombiningusedpre-trainedDenseNetextractmorphologicalidentifyrelevantlinkedapplied1-dimensionalconvolutionalneuralCNNfollowedlayerwiserelevancepropagationLRPFinallyconcatenatedacrossmodalitiesfedextremegradientboostingXGBoosttree-basedclassifierclassifyhealthycontrolResults:Experimentalevaluationclinicaldatasetdemonstratedcomparedoutcomesmodalityindividuallyapproachperformedaccuracy7901%Conclusion:basedselectsefficientlyfuseobtainscoresAdditionallyusingExplainableAIablepinpointvalidatecontributedprovidingnecessaryinterpretationbehindfindingsMulti-modalgenomicdataexplainableartificialintelligenceconnectivityFNCgenetics

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