Pubmed du 08/10/23
1. Abdi M, Aliyev E, Trost B, Kohailan M, Aamer W, Syed N, Shaath R, Gandhi GD, Engchuan W, Howe J, Thiruvahindrapuram B, Geng M, Whitney J, Syed A, Lakshmi J, Hussein S, Albashir N, Hussein A, Poggiolini I, Elhag SF, Palaniswamy S, Kambouris M, de Fatima Janjua M, Tahir MOE, Nazeer A, Shahwar D, Azeem MW, Mokrab Y, Aati NA, Akil A, Scherer SW, Kamal M, Fakhro KA. Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study. Genome Med;2023 (Oct 7);15(1):81.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study-a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research. METHODS: In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families. RESULTS: Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts. CONCLUSIONS: This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community.
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2. Lakhan A, Mohammed MA, Abdulkareem KH, Hamouda H, Alyahya S. Autism Spectrum Disorder detection framework for children based on federated learning integrated CNN-LSTM. Comput Biol Med;2023 (Oct 4);166:107539.
The incidence of Autism Spectrum Disorder (ASD) among children, attributed to genetics and environmental factors, has been increasing daily. ASD is a non-curable neurodevelopmental disorder that affects children’s communication, behavior, social interaction, and learning skills. While machine learning has been employed for ASD detection in children, existing ASD frameworks offer limited services to monitor and improve the health of ASD patients. This paper presents a complex and efficient ASD framework with comprehensive services to enhance the results of existing ASD frameworks. Our proposed approach is the Federated Learning-enabled CNN-LSTM (FCNN-LSTM) scheme, designed for ASD detection in children using multimodal datasets. The ASD framework is built in a distributed computing environment where different ASD laboratories are connected to the central hospital. The FCNN-LSTM scheme enables local laboratories to train and validate different datasets, including Ages and Stages Questionnaires (ASQ), Facial Communication and Symbolic Behavior Scales (CSBS) Dataset, Parents Evaluate Developmental Status (PEDS), Modified Checklist for Autism in Toddlers (M-CHAT), and Screening Tool for Autism in Toddlers and Children (STAT) datasets, on different computing laboratories. To ensure the security of patient data, we have implemented a security mechanism based on advanced standard encryption (AES) within the federated learning environment. This mechanism allows all laboratories to offload and download data securely. We integrate all trained datasets into the aggregated nodes and make the final decision for ASD patients based on the decision process tree. Additionally, we have designed various Internet of Things (IoT) applications to improve the efficiency of ASD patients and achieve more optimal learning results. Simulation results demonstrate that our proposed framework achieves an ASD detection accuracy of approximately 99% compared to all existing ASD frameworks.
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3. O’Reilly C, Huberty S, van Noordt S, Desjardins J, Wright N, Scorah J, Webb SJ, Elsabbagh M. EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder. Mol Autism;2023 (Oct 7);14(1):37.
BACKGROUND: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy. METHODS: We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N = 92) or elevated likelihood for ASD (N = 90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between cortical sources of EEG during video watching using the corrected imaginary part of phase-locking values. RESULTS: Our main analysis found no significant association between functional connectivity and ASD, showing only significant effects for age, sex, age-sex interaction, and site. Given these null results, we performed an exploratory analysis and observed, at 12 months, a negative correlation between functional connectivity and ADOS calibrated severity scores for restrictive and repetitive behaviors (RRB). LIMITATIONS: The small sample of ASD participants inherent to sibling studies limits diagnostic group comparisons. Also, results from our secondary exploratory analysis should be considered only as potential relationships to further explore, given their increased vulnerability to false positives. CONCLUSIONS: These results are inconclusive concerning an association between EEG functional connectivity and ASD in infancy. Exploratory analyses provided preliminary support for a relationship between RRB and functional connectivity specifically, but these preliminary observations need corroboration on larger samples.
