Extended Data Fig. 3: AHBA transcriptional components were reproducible in independent PsychENCODE control data, with differential spatial expression in autism.

a, Gene weights from dimension reduction applied to group-averaged bulk RNA-seq measurements from 11 cortical regions in N = 54 healthy control brains from the PsychENCODE dataset36 were correlated with gene weights from the components of the AHBA (derived by DME in the 180-region HCP-MMP parcellation), showing that the genetic profiles of AHBA C1, C2, and C3 were reproduced by PsychENCODE C1, C2, and C4, respectively (highlighted in green). b, Regional scores of PsychENCODE C1, C2 and C4 were also correlated with region scores of AHBA C1, C2 and C3, showing that the matching genetic profiles correspond to matching spatial expression patterns. c, Variance explained by the first five components of each dataset, showing that AHBA C3 and PsychENCODE C4 account for similar proportions of variance (6.5% and 7.1%, respectively). d, 1st row: Cortical maps of AHBA C1-C3 in the same 11 regions sampled in the PsychENCODE data. 2nd row: Cortical maps of PsychENCODE C1, C2, and C4 demonstrating their spatial similarity to AHBA C1-C3. 3rd row: Gene weights from the PsychENCODE healthy control data were projected onto transcriptional data of cases with autism spectrum disorder (ASD; N = 58) from the same dataset, demonstrating lower regional expression at the positive (red) pole of each component in the ASD cases compared to healthy controls. e, Distributions of regional scores for C1, C2 and C4, computed on group-average healthy controls as in a-d and projected to individual donor brains in the PsychENCODE dataset, demonstrating significant case-control differential expression for regions at the positive poles of C1-C3. T-tests of case-control differences were corrected for multiple comparisons across all 33 tests; boxplots represent the median, first, and third quartiles with whiskers showing 1.5 * inter-quartile range; *, **, *** indicate FDR-corrected two-sided p-value < 0.05, 0.01, 0.001 respectively. Region names refer to the sampled Brodmann Areas (BA)36: Visual = BA17, Temporal Pole = BA38, Somatosensory = BA3-1-2-5, Motor = BA4-6, Anterior Cingulate = BA24, Prefrontal = BA9, Broca′s Area = BA44-45, Fusiform Gyrus = BA20-37, Auditory = BA41-42-22, Lateral Parietal = BA39-40, Dorsal Parietal = BA7.