form = ~ (1|Dx) + (1|Cell.Type) + (1|Sex) + (1|Donor)
vp = fitExtractVarPartModel( vobj, form, metadata)
plotVarPart(sortCols(vp))

duplicateCorrelation

metadata2$Interaction = with(metadata, gsub(" ", ".", paste( Dx, Cell.Type, sep='_')))

form = ~ Interaction - 1 + MEF + Fibroblast + Sex

design = model.matrix( form , metadata2)

cons_separate_cell_type = makeContrasts( 
    SZNPC = InteractionSZ_NPC - InteractionCT_NPC, 
    SZNeuron = InteractionSZ_6_wk_FB_neuron - InteractionCT_6_wk_FB_neuron,  
    SZinteraction = (InteractionSZ_NPC - InteractionCT_NPC) - (InteractionSZ_6_wk_FB_neuron - InteractionCT_6_wk_FB_neuron),
    levels = colnames(design))

fit = lmFit( vobj, design, block=metadata$Donor, correlation=dupcor$consensus )
fit2 <- contrasts.fit(fit, cons_separate_cell_type)
fit2 = eBayes(fit2)

Dream

form = ~ Interaction - 1 + MEF + Fibroblast + Sex + (1|Donor)
# form = ~ Interaction  + MEF + Fibroblast + Sex + (1|Donor)

# SZNPC = InteractionSZ_NPC - InteractionCT_NPC, 
L_npc = getContrast( vobj, form, metadata2, "InteractionSZ_NPC")
L_npc['InteractionCT_NPC'] = -1

# SZNeuron = InteractionSZ_6_wk_FB_neuron - InteractionCT_6_wk_FB_neuron, 
L_neuron = getContrast( vobj, form, metadata2, "InteractionSZ_6_wk_FB_neuron")
L_neuron['InteractionCT_6_wk_FB_neuron'] = -1 

fitDream_npc = dream( vobjMM, form, metadata2, L_npc) 
fitDream_neuron = dream( vobjMM, form, metadata2, L_neuron)

Analysis of neuron

Compare p-values from dream and duplicateCorrelation

compare to eQTL

Analysis of NPC

compare to eQTL

Enrichments

dupcor NPC

NGenes Direction PValue FDR
KEGG_OXIDATIVE_PHOSPHORYLATION 108 Down 8.6e-07 0.0083
c2.KEGG_OXIDATIVE_PHOSPHORYLATION 105 Down 8.9e-07 0.0083
c5.GO_LYTIC_VACUOLE_MEMBRANE 228 Down 1.9e-06 0.0120
kirov_psych.ed.set_Pre-synaptic_active_z 164 Down 3.5e-06 0.0131
kirov_synaptic.sets_Pre-synaptic_active_ 164 Down 3.5e-06 0.0131
h.HALLMARK_OXIDATIVE_PHOSPHORYLATION 198 Down 6.1e-06 0.0166
c5.GO_CLATHRIN_VESICLE_COAT 23 Down 6.2e-06 0.0166
kirov_psych.ed.set_Pre-synapse 397 Down 7.3e-06 0.0170
c5.GO_SMOOTHENED_SIGNALING_PATHWAY 65 Up 8.2e-06 0.0171
c2.REACTOME_NEF_MEDIATES_DOWN_MODULATION 16 Down 9.5e-06 0.0177
c5.GO_REGULATION_OF_DEFENSE_RESPONSE_TO_ 23 Down 1.2e-05 0.0201
Nef-mediates_down_modulation_of_cell_su 17 Down 1.4e-05 0.0201
The_citric_acid_(TCA)_cycle_and_respira 117 Down 1.5e-05 0.0201
smoothened signaling pathway 51 Up 1.5e-05 0.0201
c2.REACTOME_THE_ROLE_OF_NEF_IN_HIV1_REPL 21 Down 1.6e-05 0.0201
The_role_of_Nef_in_HIV-1_replication_an 22 Down 2.1e-05 0.0224
regulation of defense response to virus 22 Down 2.1e-05 0.0224
c2.REACTOME_GLUCOSE_METABOLISM 58 Down 2.3e-05 0.0224
Gluconeogenesis 27 Down 2.6e-05 0.0224
c5.GO_NADH_METABOLIC_PROCESS 30 Down 3.0e-05 0.0224
DARPP-32_events 23 Down 3.1e-05 0.0224
c2.REACTOME_GLUCONEOGENESIS 28 Down 3.3e-05 0.0224
KEGG_PARKINSON’S_DISEASE 109 Down 3.5e-05 0.0224
embryonic skeletal system morphogenesis 64 Up 3.5e-05 0.0224
c2.REACTOME_TCA_CYCLE_AND_RESPIRATORY_EL 114 Down 3.6e-05 0.0224
c5.GO_VACUOLAR_MEMBRANE 499 Down 3.7e-05 0.0224
kirov_control.ed.set_Recycling_Endosomes 58 Down 3.7e-05 0.0224
c2.REACTOME_RESPIRATORY_ELECTRON_TRANSPO 63 Down 3.8e-05 0.0224
Respiratory_electron_transport 65 Down 3.8e-05 0.0224
kegg_Parkinson’s_disease 110 Down 3.9e-05 0.0224

dupcor neuron

NGenes Direction PValue FDR
c5.GO_BITTER_TASTE_RECEPTOR_ACTIVITY 13 Up 7.5e-13 1.4e-08
c5.GO_TASTE_RECEPTOR_ACTIVITY 16 Up 5.0e-11 4.7e-07
c5.GO_DETECTION_OF_CHEMICAL_STIMULUS_INV 17 Up 2.3e-10 1.5e-06
Class_C 24 Up 1.6e-07 7.6e-04
CMC-modules_yellow 423 Up 2.3e-07 8.6e-04
c5.GO_SENSORY_PERCEPTION_OF_TASTE 26 Up 3.4e-07 1.1e-03
sensory perception of taste 26 Up 5.0e-07 1.3e-03
abnormal_maxillary_shelf_morphology 18 Up 8.8e-06 2.1e-02
abnormal_pterygoid_process_morphology 14 Up 1.5e-05 3.1e-02
c2.REACTOME_DARPP_32_EVENTS 23 Down 1.9e-05 3.5e-02
DARPP-32_events 23 Down 2.3e-05 3.8e-02
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 Down 2.4e-05 3.8e-02
abnormal_palate_bone_morphology 30 Up 4.3e-05 6.2e-02
c2.FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN 46 Down 6.6e-05 8.1e-02
c2.HORTON_SREBF_TARGETS 24 Up 7.1e-05 8.1e-02
c7.GSE16385_IFNG_TNF_VS_IL4_STIM_MACROPH 180 Down 7.3e-05 8.1e-02
c7.GSE22886_NAIVE_CD4_TCELL_VS_DC_DN 180 Down 7.3e-05 8.1e-02
Cholesterol_biosynthesis 21 Up 1.1e-04 1.2e-01
c2.REACTOME_CHOLESTEROL_BIOSYNTHESIS 20 Up 1.2e-04 1.2e-01
c2.SCHMIDT_POR_TARGETS_IN_LIMB_BUD_UP 23 Up 1.3e-04 1.2e-01
Metabotropic_glutamate_receptor_group_II 38 Down 1.3e-04 1.2e-01
MHC protein complex 10 Down 1.5e-04 1.3e-01
c5.GO_MHC_PROTEIN_COMPLEX 11 Down 1.7e-04 1.4e-01
COP9 signalosome 29 Down 1.9e-04 1.4e-01
KEGG_PARKINSON’S_DISEASE 109 Down 2.1e-04 1.4e-01
CMC-modules_black 625 Down 2.1e-04 1.4e-01
c5.GO_COP9_SIGNALOSOME 28 Down 2.2e-04 1.4e-01
KEGG_SYNAPTIC_VESICLE_CYCLE 57 Down 2.2e-04 1.4e-01
kegg_Synaptic_vesicle_cycle 57 Down 2.2e-04 1.4e-01
kegg_Parkinson’s_disease 110 Down 2.3e-04 1.4e-01

dream NPC

NGenes Direction PValue FDR
KEGG_OXIDATIVE_PHOSPHORYLATION 108 Down 3.8e-08 0.00040
c2.KEGG_OXIDATIVE_PHOSPHORYLATION 105 Down 4.2e-08 0.00040
kirov_psych.ed.set_Pre-synaptic_active_z 164 Down 1.6e-07 0.00076
kirov_synaptic.sets_Pre-synaptic_active_ 164 Down 1.6e-07 0.00076
kirov_psych.ed.set_Pre-synapse 397 Down 6.0e-07 0.00177
c5.GO_CLATHRIN_VESICLE_COAT 23 Down 6.2e-07 0.00177
c5.GO_LYTIC_VACUOLE_MEMBRANE 228 Down 6.6e-07 0.00177
h.HALLMARK_OXIDATIVE_PHOSPHORYLATION 198 Down 8.2e-07 0.00193
The_citric_acid_(TCA)_cycle_and_respira 117 Down 1.2e-06 0.00247
c2.REACTOME_GLUCOSE_METABOLISM 58 Down 3.4e-06 0.00430
Respiratory_electron_transport_ATP_synt 80 Down 3.5e-06 0.00430
Respiratory_electron_transport 65 Down 3.6e-06 0.00430
c2.REACTOME_RESPIRATORY_ELECTRON_TRANSPO 78 Down 3.7e-06 0.00430
c2.REACTOME_RESPIRATORY_ELECTRON_TRANSPO 63 Down 3.7e-06 0.00430
c2.REACTOME_TCA_CYCLE_AND_RESPIRATORY_EL 114 Down 3.7e-06 0.00430
KEGG_PARKINSON’S_DISEASE 109 Down 3.8e-06 0.00430
c2.REACTOME_NEF_MEDIATES_DOWN_MODULATION 16 Down 4.0e-06 0.00430
kegg_Parkinson’s_disease 110 Down 4.3e-06 0.00430
c5.GO_REGULATION_OF_DEFENSE_RESPONSE_TO_ 23 Down 4.8e-06 0.00430
c2.REACTOME_EGFR_DOWNREGULATION 24 Down 5.2e-06 0.00430
Gluconeogenesis 27 Down 5.2e-06 0.00430
c5.GO_PROTON_TRANSPORTING_TWO_SECTOR_ATP 42 Down 5.4e-06 0.00430
Nef-mediates_down_modulation_of_cell_su 17 Down 6.0e-06 0.00430
c2.KEGG_PARKINSONS_DISEASE 106 Down 6.2e-06 0.00430
Glucose_metabolism 56 Down 6.2e-06 0.00430
c2.REACTOME_THE_ROLE_OF_NEF_IN_HIV1_REPL 21 Down 6.4e-06 0.00430
kirov_psych.ed.set_Synaptic_vesicle 315 Down 6.4e-06 0.00430
kirov_synaptic.sets_Synaptic_vesicle 315 Down 6.4e-06 0.00430
c2.REACTOME_GLUCONEOGENESIS 28 Down 6.8e-06 0.00436
c5.GO_NADH_METABOLIC_PROCESS 30 Down 8.3e-06 0.00499

dream neuron

NGenes Direction PValue FDR
c5.GO_BITTER_TASTE_RECEPTOR_ACTIVITY 13 Up 3.2e-13 6.0e-09
c5.GO_TASTE_RECEPTOR_ACTIVITY 16 Up 2.7e-11 2.5e-07
c5.GO_DETECTION_OF_CHEMICAL_STIMULUS_INV 17 Up 1.2e-10 7.7e-07
Class_C 24 Up 1.1e-07 4.4e-04
CMC-modules_yellow 423 Up 1.2e-07 4.4e-04
c5.GO_SENSORY_PERCEPTION_OF_TASTE 26 Up 2.4e-07 7.5e-04
sensory perception of taste 26 Up 4.1e-07 1.1e-03
c2.REACTOME_DARPP_32_EVENTS 23 Down 6.7e-06 1.6e-02
c2.KIM_ALL_DISORDERS_CALB1_CORR_UP 517 Down 8.6e-06 1.6e-02
DARPP-32_events 23 Down 8.6e-06 1.6e-02
c2.FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN 46 Down 1.3e-05 2.3e-02
c7.GSE22886_NAIVE_CD4_TCELL_VS_DC_DN 180 Down 1.8e-05 2.8e-02
c7.GSE16385_IFNG_TNF_VS_IL4_STIM_MACROPH 180 Down 2.1e-05 3.0e-02
KEGG_SYNAPTIC_VESICLE_CYCLE 57 Down 2.4e-05 3.0e-02
kegg_Synaptic_vesicle_cycle 57 Down 2.4e-05 3.0e-02
c2.HORTON_SREBF_TARGETS 24 Up 3.0e-05 3.4e-02
c5.GO_PROTON_TRANSPORTING_TWO_SECTOR_ATP 42 Down 3.2e-05 3.4e-02
KEGG_OXIDATIVE_PHOSPHORYLATION 108 Down 3.3e-05 3.4e-02
c2.SCHMIDT_POR_TARGETS_IN_LIMB_BUD_UP 23 Up 3.7e-05 3.6e-02
c5.GO_UBIQUITIN_LIKE_PROTEIN_CONJUGATING 29 Down 4.3e-05 4.1e-02
Cholesterol_biosynthesis 21 Up 4.7e-05 4.2e-02
c2.REACTOME_CHOLESTEROL_BIOSYNTHESIS 20 Up 5.1e-05 4.2e-02
KEGG_PARKINSON’S_DISEASE 109 Down 5.2e-05 4.2e-02
c2.KEGG_OXIDATIVE_PHOSPHORYLATION 105 Down 5.4e-05 4.2e-02
kegg_Parkinson’s_disease 110 Down 5.8e-05 4.4e-02
abnormal_maxillary_shelf_morphology 18 Up 7.2e-05 4.8e-02
c2.SESTO_RESPONSE_TO_UV_C0 98 Down 7.8e-05 4.8e-02
Metabotropic_glutamate_receptor_group_II 38 Down 7.9e-05 4.8e-02
respiratory electron transport chain 97 Down 8.0e-05 4.8e-02
gws3k-8.6_Non-melanoma_skin_cancer 15 Down 8.2e-05 4.8e-02

Compare NPC

Compare neuron

Publication plot