Evidence map›Paper›PMID 40899917›Full record

ArticleGigaScience2025

High-precision machine learning identifies a reproducible functional connectivity signature of autism spectrum diagnosis in a subset of individuals.

Natasha Clarke, Sebastian Urchs, Hien Duy Nguyen, Clara Moreau, Christian Dansereau, Angela Tam, Alan C Evans, Lune Bellec

Abstract read
In one paragraph

Article in GigaScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Natasha ClarkeCentre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, QC H3W 1W5 Montréal, Canada.ORCID 0000-0003-2455-3614
Sebastian UrchsCentre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, QC H3W 1W5 Montréal, Canada.ORCID 0000-0001-5504-8579
Hien Duy NguyenSchool of Computing, Engineering and Mathematical Sciences, La Trobe University, VIC 3086 Bundoora, Australia.ORCID 0000-0002-9958-432X
Clara MoreauDépartement de Psychiatrie et d'Addictologie, Université de Montréal, QC H3T 1J4  Montréal, Canada.ORCID 0000-0001-6217-731X
Christian DansereauCentre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, QC H3W 1W5 Montréal, Canada.ORCID 0000-0003-3363-1901
Angela TamCentre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, QC H3W 1W5 Montréal, Canada.ORCID 0000-0001-6752-5707
Alan C EvansMontreal Neurological Institute and Hospital, McGill University, QC H3A 2B4 Montreal, Canada.ORCID 0000-0003-3841-6098
Lune BellecCentre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, QC H3W 1W5 Montréal, Canada.ORCID 0000-0002-9111-0699

Funding

Australian Research Council DE170101134Australian Research Council DP180101192Azrieli Foundation
6 · The paper itself

Abstract

backgroundDiscovery of predictive biomarkers is essential for understanding the neurobiological underpinnings of autism spectrum diagnosis (ASD) and improving identification. Resting-state functional connectivity analyses of individuals with ASD have established sensitivity of brain connectivity at the group level. However, the extensive heterogeneity in ASD limits the translation of these findings into reliable individual-level biomarkers. We analyzed the Autism Brain Imaging Data Exchange 1 and 2 datasets, calculating Pearson's correlation-based functional connectivity across 18 brain networks. Using transductive conformal prediction, a machine learning approach that assigns confidence scores to predictions based on conformality to known classes, we classified individuals with ASD and neurotypical controls.

resultsBy combining predictors into an ensemble using hierarchical agglomerative clustering, we identified a signature that confers a more than 7-fold increase in individual risk of ASD, yet is still identified in an estimated 1 in 200 individuals in the general population. The individual risk conferred by the model is increased 4-fold over that of previously published imaging models and outperforms the current state of the art in precision for ASD classification. The high-risk signature was characterized by underconnectivity of transmodal brain networks, including the frontoparietal and basal ganglia network, and subcomponents of the limbic and default mode networks.

conclusionsA highly targeted prediction model can identify a subset of functional connectivity alterations that confer high risk for ASD at the individual level, which may be masked by traditional machine learning models due to ASD heterogeneity. Results could help disentangle the multitude of etiological pathways and behavioral symptoms that challenge our understanding of ASD by focusing on highly penetrant connectivity signatures.

Indexed as

Autism Spectrum DisorderBrainConnectomeMachine LearningAdolescentChildFemaleHumansMagnetic Resonance ImagingMaleNerve Netautism spectrum diagnosisresting-state functional connectivitytransductive conformal prediction

Identifiers

PMID40899917
PMCPMC12406215

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.