Discovery sample: ABIDE I and II

For discovery analyses, we examined the R-fMRI dataset with one of the largest number of females and males in both the autism and the NT groups available to date, selected from the Autism Brain Imaging Data Exchange (ABIDE) repositories ABIDE I and II [22, 23]. The final ABIDE I and II dataset of N = 1019 included N = 82 females with autism, N = 362 males with autism, N = 166 neurotypical females (NT F), and N = 409 neurotypical males (NT M), aggregated across 13 sites. Specific selection criteria are described in Supplementary Methods in the Additional file 1 and depicted as a figure in the Additional file 1: Figure S1. Briefly, we selected cases between 7 and 18 years of age (the ages most represented across ABIDE sites), with MRI data successfully completing brain image co-registration and transformation to standard space, with FIQ between 70 and 148 and with mean framewise displacement (mFD) [54] within three times the interquartile range (IQR) + the third quartile (Q3) of the sample (i.e., mFD 0.39 mm). Further steps included matching for mean age across groups, as well as for mFD and IQ within diagnostic groups. This latter step limited the number of exclusions while keeping average group motion low (mFD < 0.2 mm) and sampling biases that may result when matching neurodevelopmental conditions to NT around intrinsic features such as IQ [55, 56]. At each step, any sites with less than three individual datasets per diagnostic/sex groups were excluded. Demographics and characteristics of this sample are summarized in Table ​Table11 and in Supplementary Methods in the Additional file 1.

Characterization of sample merged across ABIDE I and II Cluster masks are overlaid on inflated brain maps generated by BrainNet Viewer

ABIDE Autism Brain Imaging data exchange, ADI-R Autism Diagnostic Interview-Revised, ADOS-2 Autism Diagnostic Observation Schedule-2, ASD Autism Spectrum Disorder, CSS Calibrated Severity Score, F females, IQ intellectual quotient, M males, Mean FD mean framewise displacement [54]; NT neurotypical, RRB restricted repetitive behaviors

^aABIDE I data collections: KKI, Leuven2, NYU, OHSU, Pitt, SDSU, Stanford, UCLA1, UM1, and Yale. ABIDE II data collections: ABIDEII-GU1, ABIDEII-KKI1, ABIDEII-KKI2, ABIDEII-NYU1, ABIDEII-OHSU1, ABIDEII-SDSU1, ABIDEII-UCD1 and ABIDEII-UCLA1. KKI and ABIDEII-KKI1, NYU and ABIDEII-NYU1, SDSU and ABIDEII-SDSU1, OHSU and ABIDEII-OHSU1 and UCLA1 and ABIDEII-UCLA1 were merged into one site across ABIDE I and ABIDE II collections

^bFIQ was available for 362 males with ASD (2 missing from UM1, ABIDEII-SDSU1), 81 females with ASD (1 missing from ABIDEII-GU1), 407 neurotypical males (NT M) [3 missing from ABIDEII-GU1 (N = 1), UM1 (N = 2)] and all 166 NT females (NT F)

^cVIQ was available for 315 males with ASD (47 missing; KKI (N = 14), ABIDEII-OHSU1 (N = 22), OHSU (N = 9), ABIDEII-SDSU1 (N = 1); ABIDEII-UCLA1 (N = 1), 70 females with ASD [12 missing, ABIDEII-GU1 (N = 1), KKI (N = 4), ABIDEII-OHSU1 (N = 7)], 351 NT M [59 missing; ABIDEII-GU1 (N = 1), KKI (N = 23), OHSU (N = 15), ABIDEII-OHSU1 (N = 20)], and 139 NT F [27 missing; KKI (N = 8), ABIDEII-OHSU1 (N = 19)]

^dPIQ was available for 306 males with ASD [56 missing; ABIDEII-GU1 (N = 9), KKI (N = 14), OHSU (N = 9), ABIDEII-OHSU1 (N = 22), ABIDEII-UCLA1 (N = 1), UM1, (N = 1)], 67 females with ASD [15 missing; ABIDEII-GU1 (N = 4), KKI (N = 4), ABIDEII-OHSU1 (N = 7)], 349 NT M [61 missing; ABIDEII-GU1 (N = 1), KKI (N = 23), OHSU (N = 15), ABIDEII-OHSU1 (N = 20), UM1, (N = 2)], 139 NT F [27 missing; KKI (N = 8), ABIDEII-OHSU1 (N = 19)]

^eADI-R Social scores were available for 317 males with ASD [45 missing; ABIDEII-GU1 (N = 1), Leuven2 (N = 10), NYU (N = 3), ABIDEII-NYU1 (N = 1), SDSU (N = 2), ABIDEII-UCD1 (N = 11), ABIDEII-UCLA1 (N = 14), UM1, (N = 2), Yale (N = 3)] and 68 females with ASD [14 missing; ABIDEII-GU1 (N = 1), ABIDEII-KKI1 (N = 2), Leuven2 (N = 3), NYU (N = 1), Pitt (N = 1), ABIDEII-UCD1 (N = 3), ABIDEII-UCLA1 (N = 1), Yale (N = 2)]

^fADI-R Communication and RRB scores were available for 318 males with ASD [45 missing; ABIDEII-GU1 (N = 1), Leuven2 (N = 10), NYU (N = 2), ABIDEII-NYU1 (N = 1), SDSU (N = 2), ABIDEII-UCD1 (N = 11), ABIDEII-UCLA1 (N = 14), UM1, (N = 2), Yale (N = 3)] and 68 females with ASD [14 missing; ABIDEII-GU1 (N = 1), ABIDEII-KKI1 (N = 2), Leuven2 (N = 3), NYU (N = 1), Pitt (N = 1), ABIDEII-UCD1 (N = 3), ABIDEII-UCLA1 (N = 1), Yale (N = 2)]

^gADOS-Gotham Social-Affect was available for 261 males with ASD [101 missing; ABIDEII-GU1 (N = 27), ABIDEII-KKI1 (N = 13), Leuven2 (N = 10), NYU (N = 7), OHSU (N = 11), Pitt (N = 8), SDSU (N = 8), Stanford (N = 6), ABIDEII-UCLA1 (N = 5), UM1 (N = 6), Yale (N = 1)] and 55 females with ASD [27 missing; ABIDEII-GU1 (N = 6), ABIDEII-KKI1 (N = 7), Leuven2 (N = 3), ABIDEII-OHSU1 (N = 1), Pitt (N = 4), Stanford (N = 1), ABIDEII-UCD1 (N = 1), UCLA1 (N = 1), UM1 (N = 3)]

^hADOS-Gotham RRB was available for 264 males with ASD [98 missing; ABIDEII-GU1 (N = 27), ABIDEII-KKI1 (N = 13), Leuven2 (N = 10), NYU (N = 7), OHSU (N = 11), Pitt (N = 8), SDSU (N = 8), Stanford (N = 3), ABIDEII-UCLA1 (N = 5), UM1 (N = 6), Yale (N = 1)] and 56 females with ASD [26 missing; ABIDEII-GU1 (N = 6), ABIDEII-KKI1 (N = 7), Leuven2 (N = 3), ABIDEII-OHSU1 (N = 1), Pitt (N = 4), ABIDEII-UCD1 (N = 1), UCLA1 (N = 1), UM1 (N = 3)]

ⁱADOS-Gotham calibrated severity scores [65] were available for 347 males with ASD (15 missing) and 77 females with ASD (5 missing)

^jAttention Deficit Hyperactivity Disorder (ADHD; N = 63); anxiety disorder (N = 22); Oppositional Defiant Disorder (ODD; N = 17); mood disorder (N = 11); Tourettes/Tics (N = 6); Obsessive–Compulsive Disorder (OCD; N = 6); enuresis (N = 8); encopresis (N = 4); developmental articulation disorder (N = 1); developmental dyslexia (N = 1); sensory integration disorder (N = 1)

^kADHD (N = 17); anxiety disorder (N = 7); ODD (N = 10); mood disorder (N = 2); OCD (N = 2); enuresis (N = 2); encopresis (N = 1). The three group means were compared with ANOVA tests (or Kruskal–Wallis test in the case of non-parametric mean FD) followed by post-hoc pairwise t test comparisons (or Mann–Whitney U tests in the case of non-parametric mean FD) when statistically significant (significance cut-off set at p < 0.05)