Part 2: Cov Cim Cim Cim Cim Cim Cim Cim Cim Cim ntawm Cortical Thiab Subcortical Regions Associated Nrog Tib Neeg Nco

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Pls nyem qhov no mus rau Part 1

Pls nyem qhov no mus rau Ntu 3

Cov ntaub ntawv tshuaj xyuas ntawm caj ces kos npe

Txhawm rau ntsuas tus naj npawb ntawm cov neeg sib tw gene "hits" rau covncokev tsom xam, peb tau ua cov ntaub ntawv tshuaj xyuas rau txhua daim ntawv teev cov noob CL thiab suav cov noob caj noob ces-nco(piv txwv li, qhov zoo tiag tiag) lossis cov koom haum ua haujlwm gene-motor (piv txwv li, qhov zoo tsis raug; Fig. 1F). Qhov no tau ua los ntawm kev tshuaj xyuas cov ntaub ntawv sim hauv Google Scholar, los ntawm kev tshawb nrhiav: ["gene name" THIAB ("nco" OR "amnesia" OR "Alzheimer's" OR "dementia")] thiab ["gene name" THIAB ("motor ua haujlwm" LOSSIS "motor coordination" LOSSIS "locomotor" OR "ataxia" LOSSIS "motor learning" LOSSIS "Parkin-son's" OR "Huntington's")], raws li. Tib yam tau rov ua dua rau kev tsom xam lub cev muaj zog rau qhov tseeb qhov zoo thiab qhov tsis zoo. Cov teeb meem raug xaiv rau kev tshawb nrhiav lo lus tseem ceeb vim tias lawv muaj qhov tsis zoo hauv kev nco thiab lub cev muaj zog ua haujlwm. Cov pov thawj muaj zog suav nrog cov kev tshawb fawb uas ua haujlwm hauv vivo gene manipulations, mutants thiab pharmacological cuam tshuam, thaum cov pov thawj tsis muaj zog suav nrog kev suav cov noob caj noob ces, kev tshawb fawb hauv vitro, kev tshawb fawb txog cov noob sib txawv thiab tib neeg cov ntaub ntawv tshawb fawb. Cov ntaub ntawv pov thawj tsuas yog suav tias yog kev lees paub yog tias nws cuam tshuam rau thaj tsam ntawm lub hlwb, piv txwv li, cortical lossis subcortical. Yog li ntawd, cov pov thawj ntawm ib tug muab gene lub luag hauj lwm nkaus xwb nyob rau hauv lub hlwb tsis-analyzed cheeb tsam tsis tau suav. Piv txwv li, yog ib daim ntawv qhia tias lub khob tawm ntawm cov noob A nkaus xwb nyob rau hauv lub subcortex ua rau nco tsis txaus, nws yuav tsis suav ua pov thawj rau kev tsom xam ntawm cortical nco.

Cistanche tuaj yeem txhim kho kev nco

Kev sib raug zoo sib txawv hauv kev nco thiab kev txheeb xyuas lub cev muaj zog

Yog hais tias txoj kev siv tau, lub cim xeeb cov noob yuav tsum muaj qhov nruab nrab ntau dua qhov sib txheeb ntawm tus nqincotsom xam piv nrog rau lub cev muaj zog tsom xam, thiab vice versa rau lub cev muaj zog noob thiab lub cev muaj zog tsom xam r nqi. Rau txhua tus noob, qhov no tau suav los ntawm kev rho tawm nws lub cev muaj zog r tus nqi los ntawm lub cim xeeb r tus nqi, nrog qhov sib txawv zoo suav rau txoj kev ua tau zoo (Daim duab 1G). Nco ntsoov tias rau lub cim xeeb r qhov tseem ceeb los ntawm cov npe tsis zoo (piv txwv li, nco cortical -), peb muab qhov sib txawv r-tus nqi nrog -1 los qhia qhov sib txawv no raws li tus nqi zoo, zoo ib yam nrog cov npe gene zoo. Tom qab ntawd peb muab qhov nruab nrab ntawm tag nrho cov noob rau txhua qhov teeb tsa S uas txaus siab FDR q 0.05 (tib yam pib raws li kev nthuav dav daim duab qhia pom) kom tau txais xya qhov txiaj ntsig zoo li no. Raws li tus naj npawb ntawm cov noob rau ib txheej S sib txawv, peb bootstrapped tus naj npawb ntawm correlation sib txawv qhov tseem ceeb siv los xam qhov nruab nrab correlation sib txawv tus nqi ib teev. Qhov no tau ua tiav cais rau lub cim xeeb thiab kev ntsuas lub cev muaj zog los ntawm kev rov ua dua qhov sib txawv ntawm qhov sib txawv (10, 000 iterations) mus rau qhov tsawg kawg nkaus ntawm cov noob hauv lub cim xeeb (n 231) thiab lub cev muaj zog (n 146), feem. Peb pom qhov no ua ib lub thawv rau txhua qhov ntawm xya pawg, nrog rau cov ntsiab lus bootstrapped thiab 95th feem pua ​​(whiskers) rau kev nco thiab kev ntsuas lub cev muaj zog. Yog hais tias lub hauv paus tsis poob hauv 95 feem pua ​​​​ntawm kev faib tawm (piv txwv li, whiskers tsis sib tshooj nrog lub hauv paus ntawm xoom) qhov qhab nia tau suav tias txawv ntawm qhov pib (p 0.05).

Kev ntsuas txoj kev ua tau zoo hauv kev txheeb xyuas cov noob neeg sib tw

Peb ntsuas qhov ua tau zoo raws li kev txheeb xyuas cov ntaub ntawv ua ntej (Daim duab 1G). Ua li no, peb suav qhov muaj feem yuav tau txais Nncogenes per gene list. Qhov no yog ua los ntawm kev xaiv Nnconoob (tsis muaj kev hloov pauv) los ntawm lub pas dej ntawm lub cim xeeb los yognco-related disorder noob (n 644) tawm ntawm tag nrho 15,625 noob tshuaj ntsuam xyuas. Piv txwv li, yog tias 10 ntawm 10 cov noob hauv cov npe noob yog cov noob caj noob ces, qhov muaj feem yuav tshwm sim yog 1.32 10 14. Tib yam tau ua tiav raws li lub cev muaj zog thiab lub cev muaj zog muaj nuj nqi (n 104). Cov noncoCov noob tau muab tso ua ke los ntawm peb qhov chaw: (1) cov ntaub ntawv tshuaj xyuas saum toj no; (2) cov noob caj noob ces ua haujlwm "GO: 0007611 Kev Kawm lossis kev nco," los ntawm database AmiGO2 (Carbon et al., 2009; version 2.4.26, tso tawm hnub 2016-08); thiab (3) van Cauwenberghe et al. (2016). Cov genes ntsig txog lub cev muaj zog (lub cev muaj zog lossis lub cev muaj zog cuam tshuam) tau txais los ntawm (1) cov ntaub ntawv tshuaj xyuas saum toj no, (2) cov noob caj noob ces tau teeb tsa "GO: 0061743 motor learning" thiab "GO: 0061744 motor behavior" los ntawm database AmiGO2 (Carbon et al., 2009), thiab (3) Lin and Farrer (2014).

Cov qhab nia precision rau kev nco thiab kev txheeb xyuas lub cev muaj zog

Peb nug, ntawm ib tug muabncogene list nrog cov noob sau npe lincogenes, pes tsawg ntawm cov no muaj feem xyuam nrognco. Peb ntsuas qhov no los ntawm kev suav cov qhab nia precision (Daim duab 1G). Peb thawj zaug txiav txim qhov tseeb qhov zoo (piv txwv li, cov noob txuam nrog kev nco los ntawm cov ntaub ntawv tshuaj xyuas) thiab qhov tsis zoo (piv txwv li, cov noob cuam tshuam nrog lub cev muaj zog). Cov ntaub ntawv pov thawj tau hnyav li ntawd rau qhov tseeb qhov zoo, cov pov thawj muaj zog thiab cov pov thawj tsis muaj zog (txhais tau hais los saum toj no) tau txais tag nrho cov ntsiab lus thiab ib nrab-point feem. Rau txhua daim ntawv teev cov noob, peb mam li txiav txim siab tus txheej txheem qhov qhab nia los ntawm kev faib "qhov tseeb" los ntawm cov lej ntawm qhov zoo thiab qhov tsis tseeb (Eqs. 1,2). Yog tias txoj kev yog qhov tseeb, rau kev txheeb xyuas kev nco, cov qhab nia ntawm lub cim xeeb yuav tsum siab dua 0.5 thiab lub cev muaj zog hauv qab 0.5, thiab rov ua dua. Peb npaj cov qhab nia ntawm lub cim xeeb thiab lub cev muaj zog rau txhua daim ntawv teev npe (xws li ntawm 0 rau 1), thiab qhov sib txawv ntawm cov qhab nia no (xws li -1 txog 1). Qhov zoo tshaj plaws, qhov sib txawv yuav tsum ntau dua li xoom. Nyob rau hauv cov kab zauv nram qab no, Nco muaj pes tsawg leeg ntawm cov noob nrog cov pov thawj muaj zog rau nws cov koom haum nrog kev nco; Nco tus lej ntawm cov noob nrog cov pov thawj tsis muaj zog rau nws txoj kev koom nrog kev nco; Motors naj npawb ntawm cov noob nrog cov pov thawj muaj zog rau nws txoj kev koom tes nrog lub cev muaj zog; thiab Motorw tus lej ntawm cov noob nrog cov pov thawj tsis muaj zog rau nws txoj kev koom tes nrog lub cev muaj zog.

Cov ntaub ntawv muaj nyob

Tag nrho cov ntaub ntawv caj ces thiab neuroimaging siv yog muaj los ntawm AHBA (https://human.brain-map.org) thiab Neu-rosynth (https://www.neurosynth.org). Cov ntawv sau ua ntej ua cov ntawv sau tseg muaj nyob ntawm https://github.com/BMHLab/AHBAprocessing. Cov ntawv sau sib raug zoo thiab cov ntaub ntawv tawm tswv yim muaj rau kev siv tsis yog lag luam hauv Cov Ntaub Ntawv Ntxiv 1 thiab ntawm https://github.com/PK-HQ/ geneCognitionDiscovery.

Cov txiaj ntsig

AHBA thiab Neurosynth maps

Rau kev txheeb xyuas tag nrho lub hlwb neeg lausnconoob, peb thawj zaug yuav tsum tau ua qhov spatial correlation tsom xam ntawm 3D high-resolution neuroimaging thiab transcriptome maps ntawm cov neeg laus lub hlwb. Yog li ntawd, peb siv lub siab ceev, tag nrho tib neeg lub hlwb AHBA transcriptome, thiab Neurosynthncodaim ntawv qhia kev koom tes ntawm txhua lub voxel lub koom haum nrog kev nco feem ntau raws li cov ntaub ntawv nkag (Yarkoni li al., 2011).

Lub AHBA tau muab los ntawm rau lub hlwb pub dawb thiab muaj tag nrho-genome tib neeg lub hlwb gene qhia nyob rau sab laug cortical thiab subcortical cheeb tsam (N 6; Fig. 1A; saib piv txwv kev pom nyob rau hauv Extended Data Fig. 1-1; Hawrylycz li al. , 2012). Lub NeurosynthncoDaim ntawv qhia koom haum yog daim ntawv qhia kev kawm meta (N 2744) uas sawv cev rau txhua lub hlwb voxel qhov cuam tshuam raunco(as opposed to other cognitive functions), teev los ntawm qhov zoo z cov qhab nia (Daim duab 1A; saib ib tug visualization ntawm lub cim xeeb thiab lub cev muaj zog muaj nuj nqi maps nyob rau hauv Extended Data Fig. 1-2; Yarkoni li al., 2011). Nco ntsoov tias kev siv ntawmncontawm no yog hais txog kev nco feem ntau, raws li daim ntawv qhia tau tsim los ntawm kev nco txog cov kev tshawb fawb neuroimaging uas siv ntau hom kev ua haujlwm nco (Yarkoni li al., 2011). Peb tau sau npe ob daim ntawv qhia mus rau hauv ib qho chaw MNI152. Cov chaw nco hauv daim ntawv qhia kev nco tau siv los txheeb xyuas cov qauv AHBA siv tau rau cov kev txheeb xyuas qhov sib txheeb tom ntej.

Spatial zoo sib xws tsom xam

Siv cov ntaub ntawv no, peb nrhiav kev cais cov noob nrog cov txiaj ntsig zoo sib xws ntawm lawv cov noob qhia thiabncodaim ntawv qhia lub sij hawm rau cov kauj ruam tom ntej, raws li lawv feem ntau muaj feem xyuam nrog kev nco (Fox li al., 2014). Peb tau ua qhov kev soj ntsuam zoo sib xws ntawm AHBA thiab Neurosynth koom haum daim ntawv qhia sib cais rau thaj chaw cortical thiab subcortical vim lawv qhov sib txawv (saib Taw Qhia; cov npe ntawm thaj chaw cortical thiab subcortical muaj nyob rau hauv Extended DataFig. 1-3), thiab rau nco thiab lub cev muaj zog muaj nuj nqi (saib piv txwv ntawm spatial correlation nyob rau hauv daim duab 2). Txhua qhov kev tshuaj ntsuam tau muab cov npe L, uas muaj cov txiaj ntsig zoo sib xws ntawm 15,625 cov noob uas siv rau qib tom ntej (Fig. 1B).

Peb tom qab tau txheeb xyuas txhua daim ntawv teev npe L. Ib qho kev sib raug zoo qhia tau hais tias muaj ntau dua cov noob hauv cov cheeb tsam cuam tshuam raunco, thiab qhov tsis zoo correlation implies qis qhia nyob rau hauv cov cheeb tsam cuam tshuam rau kev nco. Sab saum toj -10 qhov zoo thiab tsis zoo correlated noob rau lub cim xeeb cortical thiab subcortical analyses yog qhia nyob rau hauv Table 1 (saib cov spatial correlation tus nqi ntawm tag nrho cov noob nyob rau hauv Extended Data Table 1-1). Muaj cov noob tsis zoo sib xws ntau dua li cov noob muaj txiaj ntsig zoo rau ob qho tib si cortical thiab subcortical tsom xam ntawm kev nco (Cov Ntaub Ntawv Ntxiv 1-1). Peb pom 8383 qhov zoo thiab 7243 cov noob tsis zoo rau thaj chaw cortical, thiab 7642 qhov zoo thiab 7984 cov noob tsis zoo rau thaj chaw subcortical.

Cov kab mob sib txawv ntawm cov noob caj noob ces cuam tshuam nrog cortical thiab subcortical nco

Ua raws li kev txheeb xyuas kev sib raug zoo, peb tsom los txheeb xyuas cov noob qhia cov ntaub ntawv ntsig txog cortical thiab subcortical.nconyob rau hauv ib qho kev qhia. Txhawm rau txheeb xyuas thiab txheeb xyuas cov noob caj noob ces ua haujlwm rau kev ua haujlwm lom neeg (piv txwv li, cov noob caj noob ces), peb tau txheeb xyuas txhua daim ntawv teev npe cortical thiab subcortical L nrog GSEA pre-ranked (Fig. 1C). Qhov no tau txais txiaj ntsig zoo thiab qhov tsis zoo ntawm cov noob qes, muab los ntawm cov noob zoo thiab tsis zoo ntawm L, feem. Cov noob no tau muab faib ua pawg ua haujlwm muaj feem cuam tshuam thiab tau sau tseg nrog cov ntsiab lus lom (Cline li al., 2007; Merico li al., 2010; Oesper li al., 2011).

Zuag qhia tag nrho, cortex thiab subcortex muaj cov ntsiab lus lom neeg sib txawv uas tau pom yav dhau los cuam tshuam nrog kev nco. Rau corticalnco, GSEA nthuav tawm 28 qhov zoo thiab 29 qhov tsis zoo ua rau muaj txiaj ntsig zoo ntawm cov noob. Kev pom ntawm lub network enrichment tau pom tias cov noob noob tau muab faib ua tsib pawg sib txawv (Daim duab 3; cov txiaj ntsig GSEA tiav yog nyob rau hauv Extended Data Fig. 3-1), nrog cov gene sets nyob rau hauv txhua pawg sib koom enriched noob. Cov noob no tau pom tias muaj feem xyuam nrog kev nco. Cov pawg zoo P1 muaj cov noob teeb uas cuam tshuam rau hauv lub cev tiv thaiv kab mob thiab Fc receptor signaling (Fernandez- Vizarra li al., 2012; Marin and Kipnis, 2013). P2 tau cuam tshuam rau hauv interferon-gamma signaling (Litteljohn li al., 2014), P3 hauv transmembrane calcium ion thauj thiab P4 hauv actin filament los ua ke (Krucker li al., 2000; Lamprecht, 2011). Cov pawg tsis zoo N2 muaj cov noob caj noob ces koom nrog hauv chromatin dynamics, kev tswj ntawm epigenetic, thiab kev tiv thaiv kab mob sib txawv (Kim thiab Kaang, 2017).

Rau subcorticalnco, GSEA nthuav tawm 50 qhov zoo thiab 14 qhov tsis zoo ua rau muaj txiaj ntsig zoo ntawm cov noob. Kev pom ntawm lub network enrichment tau pom tias cov noob caj noob ces tau muab faib ua peb pawg (Daim duab 4; cov txiaj ntsig GSEA tiav yog nyob rau hauv Ntxiv Cov Ntaub Ntawv Fig. 4-1). Ib yam li ntawd, cov noob caj noob ces tau pom tias muaj feem xyuam nrognco. Cov pawg zoo P1 yog cuam tshuam rau hauv kev sib kis ntawm synaptic thiab synaptic plasticity. Nws kuj suav nrog cov noob caj noob ces koom nrog hauv endocytosis thiab exocytosis, neurotransmitter secretion, potentiation mus sij hawm ntev (Stuchlik, 2014), glutamate receptor signaling, thiab neuron projection morphogenesis (Kasai li al., 2010). Cov pawg tsis zoo N1 muaj feem cuam tshuam nrog cov txheej txheem sau thiab txhais lus (Jarome thiab Helmstetter, 2014; Alberini thiab Kandel, 2015), thiab pawg N2 rau glial cell thiab oligodendrocyte sib txawv (Hertz thiab Chen, 2016; Pepper et al., 2018).

Daim duab 2. Ib qho piv txwv ntawm spatial zoo sib xws tsom xam tso zis. Cov theem qhia ntawm cov kab mob cortical saum toj kawg nkaus, GRB14, yog pom tau tias yog ib qho kev ua haujlwm ntawm Neurosynth daim ntawv qhia qhov voxel-wise muaj feem xyuam rauncomuaj nuj nqi (z tau). Kev qhia cov noob caj noob ces (y-axis) npaj tawm tsam neuroimaging daim ntawv qhia z cov qhab nia (x-axis). Txhua xim regression kab sawv cev rau txoj kab zoo tshaj plaws rau txhua tus neeg pub dawb (xim xim); cov translucent band nyob ib ncig ntawm txhua kab sawv cev rau 95 feem pua ​​​​ntawm kev ntseeg siab lub sijhawm kwv yees.

Txhawm rau txheeb xyuas qhov sib txawv thiab sib tshooj hauv cortical thiab subcortical genetic profiles, peb tau txheeb xyuas thiab pom qhov sib txawv thiab sib koom (1) cov txheej txheem lom neeg raws li qhia hauv daim duab qhia kev txhim kho, thiab (2)nconoob (piv txwv li, tag nrho cov noob muaj nyob rau hauv 1 enriched gene set; Fig. 1D). Peb pom qhov sib tshooj qis ntawm 2.5 feem pua ​​​​ntawm cov noob (N 3) thiab 9.6 feem pua ​​​​ntawm cov noob (N 135) ntawm thaj chaw cortical thiab subcortical (Fig. 5; tag nrho cov npe ntawm cov noob sib txawv thiab sib tshooj yog nyob rau hauv Extended DataFig. {{9 }}). Cov noob sib tshooj tau koom nrog hauv kev nco txog cov txheej txheem ntawm kev thauj cov protein, kev hloov pauv kev cai, synaptic plasticity thiab glutamate receptor signaling (Peng li al., 2011; Rosenberg li al., 2014; Alberini thiab Kandel, 2015; Table 2; tag nrho cov zis ntawm gene sets and genes from Top- pGene in Extended DataTable 2-1). Cov no suav nrog cov noob koom nrog hauv Arp2/3 complex, GABA thiab AMPA ligand-gated ion channels uas yog qhov tseem ceeb rau kev nco ua haujlwm (Gasbarri thiab Pompili, 2014; Basu li al., 2016; Takemoto et al., 2017; Extended Data Table { {23}}). Cortex-specific genes tau koom nrog hauv kev nco txog cov txheej txheem xws li kho DNA, kev tswj hwm epigenetic, kev tiv thaiv kab mob thiab IFN- signaling (Marin and Kipnis, 2013; Litteljohn et al., 2014; Kim and Kaang, 2017; Hou et al., 2018). ; Extended DataTable 2-1). Subcortex-specific genes koom nrog hauv neurogenesis, dendrite morphogenesis, glial cell txawv thiab myelination (Hertz thiab Chen, 2016; Kao li al.,

Daim duab 3. Enrichment map visualization rau corticalnco. Cov pawg tau sau nrog P rau qhov zoo, N rau qhov tsis zoo. Gene teeb pawg tau pom tias muaj feem xyuam nrognco. Cov pawg zoo tau cuam tshuam nrog kev tiv thaiv kab mob, kev thauj khoom calcium, thiab kev sib dhos actin filament. Cov pawg tsis zoo muaj cov noob caj noob ces koom nrog hauv chromatin dynamics thiab kev tswj hwm epigenetic. Saib Ntxiv Cov Ntaub Ntawv Daim Duab 3-1 rau tag nrho cov zis los ntawm GSEA Pre-ranked.

2018; Kua txob thiab al., 2018; Extended DataTable 2-1). Nco ntsoov tias tib lub noob caj noob ces tuaj yeem tshwm sim ob qho tib si hauv cortical-specific thiab subcortical-specific biological txheej txheem. Piv txwv li, lubncogene sets yog enriched nyob rau hauv ob qho tib si cheeb tsam, tab sis nyob rau hauv txhua rooj plaub, lub gene set enrichment yog tsav los ntawm txawv cov noob (Extended DataTable 2-1). Qhov no yog vim cov noob sib txawv tuaj yeem cuam tshuam rau, thiab yog li ua kom muaj txiaj ntsig zoo rau tib cov txheej txheem kab mob lom neeg.

Cov tub ntxhais sib txawv qhia cov noob muaj feem xyuam rau cortical thiab subcorticalnco

Txhawm rau txheeb xyuas qhov saum toj kawg nkaus -10ncocov noob uas feem ntau yuav txuas nrog tib neegncomuaj nuj nqirau kev tshawb nrhiav yav tom ntej, peb tau txheeb xyuas cov noob muaj feem xyuam rau ntau cov noob tau los saum toj no nrog LEA (Daim duab 1E; Subramanian li al., 2005; Darby li al., 2016; Fleming thiab Miller, 2016). Cov hauj lwm yav dhau los tau qhia tias cov noob caj noob ces ua kom muaj txiaj ntsig ntawm ntau cov noob caj noob ces muaj feem cuam tshuam nrog cov phenotype txheeb xyuas, piv txwv li, nco ua haujlwm hauv qhov no (Subramanian li al., 2005; Darby et al., 2016; Fleming thiab Miller, 2016). Kev sib xyaw ua ke ntawm GSEA thiab LEA yav dhau los tau ua haujlwm zoo hauv kev txheeb xyuas cov npe caj ces ntawm kev paub txog kev ua haujlwm (Thomassen li al., 2008; Ersland li al., 2012; Lee li al., 2013), suav nrog episodic thiab ua haujlwm nco (Heck et al., 2014;

Linksys et al., 2015). Peb tau siv LEA rau qhov zoo thiab qhov tsis zoo ntawm cov gene teev saum toj no, ua raws li los ntawm kev xaiv saum toj kawg nkaus -10 cov noob tshwm sim feem ntau thoob plaws cov thawj-ntug subsets ntawm cov noob. Cov noob no tau raug lees paub nrog tsiaj cov qauv ntaub ntawv, uas tau muab cais ua pov thawj muaj zog lossis tsis muaj zog txhawb kev sib txuas ntawm cov noob thiab kev nco ua haujlwm (Fig. 1F). Cov pov thawj muaj zog muaj xws li kev tswj cov noob los yog kev tshawb fawb txog kev kho tshuaj, piv txwv li, gene knock-out ua rau kev hloov pauv kev nco. Cov pov thawj tsis muaj zog suav nrog kev sib raug zoo lossis kev suav nrog kev tshawb fawb, xws li gene upregulation uas cuam tshuam nrog kev txhim kho.ncokev ua tau zoo.

Rau corticalnco, cuaj ntawm 10 qhov kev sib raug zoo genes tau raug cuam tshuam rau yav dhau losncomuaj nuj nqi(Table 3; tag nrho cov npe ntawm cortical nco genes thiab cov ntaub ntawv tshuaj xyuas Extended DataTable 3-1, ua tiav LEA cov zis nyob rau hauv Daim Ntawv Qhia Ntxiv 3-2). Genes PRKCD (Etcheberriga-ray et al., 2004; Conboy et al., 2009), RAC1 (Haditsch et al., 2009; Oh et al., 2010), LIMK1 (Todorovski et al., 2015), and CDC. Kim et al., 2014; Zhang et al., 2016) muaj kev koom tes nrog kev nco. Rau cov neeg sib tw tsis zoo sib xws, tag nrho 10 cov noob muaj cov pov thawj muaj zog txhawb nqa lawv lub luag haujlwm hauv kev nco. Cov no yog tag nrho cov noob encoding histone H4 protein, uas tau txuas nrog kev nco (Peleg li al., 2010). Deregulation ntawm histone H4 acetylation hauv cov nas muaj hnub nyoog tau txuas nrog kev nco tsis zoo, thiab rov kho cov cai no tau txhim kho lawv lub cim xeeb.

Daim duab 4. Enrichment map visualization rau subcortical nco. Cov pawg tau sau nrog P rau qhov zoo, N rau qhov tsis zoo. Gene teeb pawg tau pom tias muaj feem xyuam nrog kev nco. Cov pawg zoo tau cuam tshuam nrog kev sib kis ntawm synaptic, lub sijhawm ntev yas, glutamate signaling, thiab neurite morphogenesis. Cov pawg tsis zoo suav nrog cov noob caj noob ces koom nrog hauv kev sau thiab txhais lus thiab glial cell sib txawv. Saib Ntxiv Cov Ntaub Ntawv Daim Duab 4-1 rau tag nrho cov zis los ntawm GSEA Pre-ranked.

Rau subcortical nco, tag nrho 10 cov noob caj noob ces muaj feem cuam tshuam nrog kev ua haujlwm ntawm lub cim xeeb (Table 4; tag nrho cov npe ntawm subcortical nco noob thiab cov ntaub ntawv tshuaj xyuas hauv Cov Ntaub Ntawv Ntxiv 4-1; LEA ua rau Extended DataTable 4-2). Genes CDK5, NLGN1, RAB3A, STX1A, SNCA, SYT1, thiab UNC13A tau txuas nrog kev nco (Fujiwara et al., 2006; Yang et al., 2007; Liu et al., 2009; Guan et al., 2009; Guan et al. thiab al., 2012; Bie et al., 2014; Mishiba et al., 2014; Böhme et al., 2019). Xya tawm ntawm 10 qhov tsis zoo sib cuam tshuam cov noob caj noob ces muaj pov thawj tsis muaj zog cuam tshuam rau lawv hauv kev nco. Cov no yog cov noob encoding ribosomal subunits, uas tau sib txawv hauv cov nas uas pom zoo duancokev ua haujlwm (Wang et al., 2003; Kong et al., 2009; Winbush et al., 2012; Katz thiab Lamprecht, 2015; Oka et al., 2016; Zhang et al., 2018).