biostudies-literatureZhang JNational Natural Science Foundation of Chinabtaf629https://www.ebi.ac.uk/biostudies/studies/S-EPMC12758602biostudies-literatureUnknown42(1)<h4>Motivation</h4>Neurodegenerative disorders influence millions of people worldwide, and uncovering the pathogenesis is of urgent need. Many efforts have been made to detect or predict neurodegenerative disorders, while exploring the pathogenesis has been ignored from a systemic perspective.<h4>Results</h4>To handle this issue, we propose a novel and powerful method, referred to as Pathogenesis-aware Mutual-Assistance Classification and Regression Optimization (Pa-MACRO). First, Pa-MACRO incorporates a mutual-assistance bidirectional mapping technique with a joint-embedding fine-grained interpretability module. This can extract the intrinsic factors and their interactions of multimodal pathogenesis. Second, our method can simultaneously classify an at-risk individual and predict the seveBioinformatics (Oxford, England)Mutual learning for joint disease detection and severity prediction reveals multimodal pathogenesis for neurodegenerative disorders.PMC127586026213600462373306Schulze EHaviari AAyers KBrewer JPalou MAyres MRosen HJYurko ERiddle MMontine TRamirez JManning SRussell HBlanchard KWint DMatoush LDeStefano SReeder SMoore-Weiss JBailey RLevey AWu CKFletcher ELee EBMunic DWhite MYu MSchwarz CPietras AMay JTon AGreig-Custo MTurner RSAshe LCornell GVillar MMossa DFaircloth JScanlan MFerng NSantiago SGallagher LPetrocca EHosein CLowery SDevis YVincent SNyborg GBecerra MChiotis KZimmerman CLittle EFerman DJo TApostolova LGLah JBriglall VD'Ambrosio SLu YOSchoolcraft LLandau SFockler JHaddad LRaynes-Goldfinger DHenson RSaunders ABinder SGoldfarb DRao LHoover BWagner BSharma SPomara VElmalik WPomara NHergesheimer LMalakauskas SChen DLukose LAlosco MFleisher AMartinez NNho KSadowski MNelson ARGSullivan SJohnson KOrdor DImhansiemhonehi MJohnson NSwarm RJohnson SMartinez TStipanovich AMartinez WKertesz AMarolt ARafii MPerez GMunoz CArnold AJagust WHills ARSwitzer PScharre DWAnderson KCorona MBhan AAnderson BCrawley KMoretz LVemuri PShen LKnaack JRaji CShah RLoPresti BRamamurthy AWan YCallan MTosun-Turgut DMcColl RCheatham ESalazar RFogerty TArthur ADuffy CTong HSalazar JKnaack ABrosch JSmilowitz SBateman JLyons CRufo VLarkin KHasbani MJTrujillo SWalter SZiolkowski JKnopman DZik CMolchan SCairns NJLuu TThomas ABuckholtz NLagarde JLocke MNunes PThomas LMasterman DCabrera YSantulli RBGagliano NShaw LDawson CBaker WPacini NTran AHendrickson KWeiner MSnyder PJSchneider LAmoyaw MBlank KQuinlan LErkkinen MRivera FNewhouse PRivera EKadiri OLyron SIkner GBlack SGutierrez MSStapleton KBeckett LZamora ESchumacher MOgrocki PHernando RCereijo MWenner VKachaturian ZWebster JBates VSlazyk DRabinovici GPot SBates CLenio SHarvey DWard CBonacorsi ZFarchi MDas SMalia AAFairooz MBarger BHarrison WMunie SBergman HJahanshad NTrejo ESpicer KUffelman JGhesani NKhan ASotelo VHenkle SYong MKhan JPresto SKurvach RAssaly MJi YKantarci KBernard MSanborn VOleary KTaylor RLin ZStrong JMecca AJames OOkonkwo IPierce AHegedus SGutierrez MOkonkwo OPomper MLee VMYMba IWright EYau EFidell ABoeve BBurgos-Rivera GPolson HNudelman KDuara RHales CSano MTosun DGonzalez JWatkins ALin EGonzalez HWinterton SRobison JThao MSHendrix HJones FCapote HNeu SChoudhury PKhachaturian ZJones DDonnelly LConti CNir TMDoraiswamy PMHolvey BHill SJDuncan CKalowsky TEnglish Cvan Dyck CKreszyn KTalavera SRobbins LBFarrington LBoudreau JBissig DMcKinley ESavage KPuleio ABorowski BThompson DKoeppe RAQiu WHussen KAWeisensel TPlace PFarlow MWhite Salazar SLi HAmaza HHunt RRaya MAGood SLargent EAsbach MDevereux GWallace BAlbers CAsh SWallace KFranklin ERyan LScott CCombs MRuszkiewicz JChoe MHawk TLuong BMarti BMorris JJackson KFlenniken DBrylska MChao SVillena TJackson JO'Donnell PWatts LAtri AFaber KBurns JThompson PSteinberg EVides BMoss AFalletta JSinn MTallakson MVeronelli DJacobson AClark JZhang DWilson SWilson TZhang JClark KZhang HIntorcia DHirtreiter JClark ERaja AAmtashar FSArdolino AApuango XMJin CSilverberg NRudd TAdhikari ABasham KKahulugan QMSKaye JMontero AFatica PHellegers CTrost DYeboah SBohlman SJohns JPontone GKilliany RBoegel AOakley MRosario CSilbert LDay GVogler BMacnamara HLauture MBonomi RHopkins KBoatwright VDay TWesterhold ELongmire CFCalzavara RMahboubi PSaganis XForoud TMEllison AKelley BPejic JGarrison SZawislak RRuan ARainka MForghanian-Arani ABrown ANunez MSinai SPMHedberg CTroutman ADenis RMorales EStanhope JBarker RMorales JFrascino JShang YBarker WMasurkar ABarcelos NBrooks RGlueck AGoins LLe RGarcia-Camilo GMcGinnis SMonarrez CDemsky CWeiner MWKhera ACorreia SFriedman PMathews DLam BKenowsky SGreeson JDrake EMariotti LBenedetto JDNasrallah IDahlgren AStover CMathis NBorrie MRodriguez TThai GNieto ARose HSeshadri SAjtai BMagnuson JRobinson ELam JSalardini ETaylor JJSaito NGrossman HMathewson AHamski MMiller MJChertkow HVillemagne VOlgin SGunter JMonserratt LJenkins CGeldmacher DJones MREpperson KOlgin JAcevedo MSanders MHackenmiller BYoung IFigueroa EFigueroa CMiller MSalloway SCepeda SKapadia AVaishnavi SRamanan VPekar JLopez OMejia DRojas YGTurner KMejia KTurner JFelmlee JJRisacher SLBeigi MBurney TAsthana SMcKinzie SWong JRoss DBerner KMandal PBowser SMiller AWong TBishop JMeacham BNichols KRovere RBerman SJanavs JTaghi-Zada ZAladeen TChen MKOkhravi HHarkins KHarkins JGlittenberg MHolt MForenback DGoddard MKo AGunnoud CAjayi AMcAdams-Ortiz CDavis JCarter DTanase CReynolds BGreen RCHarte TSwiniarski JTeodoro LMechtler LO'Malley SChen SRGarcia LGondrez JMcCorkle EKovac DSSadowsky CBouchachi SGarcia ADu LDetling SDevine RLiu JMyers BLiu LPavlik VBlackburn MDenali CHNosheny RAdegoke ORowell JPlenge JLapins ASwain ARomero RSaykin AJMagana FGraff-Radford JGraff-Radford NMintz ADaSilva NAvila YHernandez MAcree AVo KHernandez RMunro CBrowning AHartman EIsip RBandy DMarian TAcothley SHarris GTacey PCPetersen RLacy KMez JHelland TAhmed TMwicigi JEchevarria JKaddurah-Daouk RCordona JHoang IJefferson SPolleys RStewart JSenjem MWiesenauer PDoyon KMasliah EPham SYushkevich PAShaffer EEmborsky ASachdev PPizzola JNwosu AJooma IGeesey EStern YSabbagh MBartha RConant CFox TVrillon AToso CRyan CRyan JGlass MUdodong IKhasnavis SShannon MToga AWWeller JDeCapo MManeval JPorsteinsson AToth Fmr Gross MPerrin RJSoleimani LSacaza KMitchell MJohnson-Acnp MBryant RBottoms JStewart WSingh ENelsen KKaplan ADonahue MMcCoubrey HDooly HFransen ERankin LGabriel GJack CRWarren SGallegos MKwang WWishnia MKippels AMacDonald SBarlow LBasheer NMayo CSingh SKorkoyah AGagnon KBuckler RKorst WEigenberger PMoncayo EBasadre SFikru SWever KHustead HJoie RSaklad AHoughtaling NYao XMandal AGamble BMasellis MPotter ZRangel MBrennan AMiddleton APotter WVaughn PBrennan EKorecka MRangel AFrolov AADiaz AStone ABrawman-Mintzer OCarpentier SGrant SSilver RMBray JGrant IAlzheimer’s Disease Neuroimaging InitiativeParand LSchwartz DArcuri DGale SWalker EPaczynski MLogan RMd GDPKusuran JChiado CLawrence KSmith CSmith AFragale DMarshall GObisesan TDonohue MPhillips EESheppard FFarshadi MSmith SElayan NThomopoulos SICooper EFenice LTariot PShaw LMChapman LClay TCrawford KLevesque IHu WKowalski NHamm TWilliams AWilliams CCrawford FPerkins AKarlawish JCarrillo MReyes PDeCarli CHonig LPatel HMahaffey JGama ATaylor-Reinwald LFrank RGermano KKReyes CReyes DLynch SHall SHoti IHall TCelmins DSmelser BLynch BPawluczyk SAloszka DPeehler TReade MAcosta MVMalone IDittrich CForero AAyo ORoglaski EWidman ABotha HLee TYBernick CBean RAisen PClanton TColvee HWebb CBoonsiri JPetrella JYork KGuzman VAshley LBUlysse ACraft HMintzer JSlaughter MEO'Connor JChaudhary MAshford MGroves AEvans KGui MCalderon SPerrin RSoleimani-Meigooni DEvans BBarnes LSeidenberg KPerrin ACarlsson CMMares IZotovic LMasdeu JHeidebrink JBernhardt HMalyarenko DMost ESood AMiller BLLiebsack CKreuger CGlennon KReid RO'Dell RRivera-Mindt MMoghekar AOgwang SErickson CHidalgo EMoore TAlbert MMattle ARivera-Delpin GYazell MLim JMwaura ISchwartz ESFox NCPatterson KBauerle HDaley ATownley RThal LMartin KKoeppe RCamarro TMoorlach KDurbin KHughes KNicole HVasanawala MMendonca CMacias LCavrel YMadison MMurphy EColeman JMcMillan MGurung MSolomon VWindon CGrill JLaBarge RDeMarco ALieb BMcCann KTarawneh RKim CKataki MAggarwal RKim EMallory JCooper HMHsiung RNath JDagerman KMcCurry CParry CVillinger TCui WReichert CLedford PHRaman RAlo TTam SChadwick MWu PHerring SJennings LWisniewski SJimenez-Knight TKlemp HCline CBassett MVanya HAbusalim AEndre RChrestensen KLowe SRobert NLowe VMalloy PSoto AO'Connell AMcDonnell MStephens SLong CPenn RWaszak JJessup AConti CCBritt KLong JTruran DNeugroschl JKormos AChirinos CRogers VLong RKing MRogers SKing KGroome AGillen LEsposito GTrncic NRogers JClayton VWilliamson JKing RSchultz OHsiao JKNguyen TTrojanowki JQHarp JReposa MNolan KNguyen MAl-Amin JNguyen LJimenez ALeader AJimenez GCampbell DRodzon BNatelson-Love MForloines MHorenkamp JfalseMutual learning for joint disease detection and severity prediction reveals multimodal pathogenesis for neurodegenerative disorders.<h4>Motivation</h4>Neurodegenerative disorders influence millions of people worldwide, and uncovering the pathogenesis is of urgent need. Many efforts have been made to detect or predict neurodegenerative disorders, while exploring the pathogenesis has been ignored from a systemic perspective.<h4>Results</h4>To handle this issue, we propose a novel and powerful method, referred to as Pathogenesis-aware Mutual-Assistance Classification and Regression Optimization (Pa-MACRO). First, Pa-MACRO incorporates a mutual-assistance bidirectional mapping technique with a joint-embedding fine-grained interpretability module. This can extract the intrinsic factors and their interactions of multimodal pathogenesis. Second, our method can simultaneously classify an at-risk individual and predict the seve2026-01-01T00:00:00Z2026 Jan2026-06-06T10:30:08.906Z2026-05-29T03:11:23.951ZS-EPMC127586024145274410.1093/bioinformatics/btaf629