Evidence map›Paper›PMID 42636188›Full record

ArticlePloS one2026

An integrated systems biology and machine learning framework for identifying potential biomarkers and pathways in autism spectrum disorder.

Sara Hosseinpoor, Hakimeh Zali, Hassan Zohrevand, Seyed Amir Mirmotalebisohi, Fariba Khodagholi, Maryam Bazrgar, Sareh Asadi, Abolhassan Ahmadiani

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Sara HosseinpoorNeuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hakimeh ZaliDepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hassan ZohrevandStudent Research Committee, Department of Biomedical Engineering and Medical Physics, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran.
Seyed Amir MirmotalebisohiStudent Research Committee, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fariba KhodagholiNeuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Maryam BazrgarNeurobiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sareh AsadiNeurobiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.ORCID https://orcid.org/0000-0003-0924-5779
Abolhassan AhmadianiNeuroscience Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutism spectrum disorders (ASD) are a group of neurodevelopmental disorders whose underlying molecular mechanisms and biological processes remain incompletely understood. In this study, we used a multi-layered systems biology approach to prioritize candidate genes and regulatory factors associated with ASD.

methodGene expression data from peripheral blood samples were obtained from the Gene Expression Omnibus (GEO) database (GSE18123). Using analyses performed in R software, differentially expressed genes (DEGs) in patients with ASD were identified (p-value < 0.05 and |log2FC| > 0.5). These DEGs were used to perform weighted gene co-expression network analysis (WGCNA) and construct a protein-protein interaction (PPI) network. By integrating the results of these network analyses with feature selection techniques (LASSO and random forest feature importance), candidate genes associated with ASD were prioritized and evaluated using qRT-PCR in the valproic acid (VPA)-induced rat model of autism. Furthermore, a gene regulatory network (GRN) was constructed to identify the regulatory factors associated with DEGs.

resultTLR8 and CASP4 were prioritized as candidate genes that may be associated with ASD, because they were located within the co-expression module that showed the strongest correlation with ASD, were identified as key nodes of the PPI network, and were selected by feature selection algorithms. Our experimental validation showed increased expression of TLR8 and CASP4 in the autism model compared with controls; TLR8 was upregulated in both the hippocampus and peripheral blood, whereas CASP4 was upregulated only in the hippocampus. Furthermore, GRN analysis identified miR-891b and miR-627-3p as potential regulators of TLR8, and miR-26b-5p as associated with CASP4.

conclusionThese findings indicate that CASP4 and TLR8, together with their associated regulatory miRNAs, may represent promising biomarkers and potential therapeutic targets for future ASD research and contribute to a better understanding of the pathophysiological mechanisms underlying ASD.

Indexed as

Autism Spectrum DisorderBiomarkersMachine LearningSystems BiologyAnimalsDisease Models, AnimalGene Expression ProfilingGene Regulatory NetworksHumansProtein Interaction MapsRatsBiomarkers

Identifiers

PMID42636188
PMCPMC13502595

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.