Identifying Genes Associated With Autism Spectrum Disorders by Random Walk Method With Significance Tests

Autism spectrum disorders (ASD) are generally defined as a development disorder typically characterized by social interaction and communication ailments and stereotyped actions due to combined genetic and environmental factors. Different critical aspects contribute to ASD, and consensus has been reached among autism researchers about its predominant genetic factors. However, the pathogenesis of ASD has not been fully revealed, and a systematic method must be developed to identify the genes related to this disease. Here, we predicted new ASD-associated genes by random walk method on the basis of prior-known ASD genes from AutDB. New genes such as RAC3, AC1 (ADCY1), PKC (PRKC) gamma, EPH receptor A5, WNT3A, calretinin, RAS-R, KLF4, and calpain 3 were found to play an irreplaceable role in ASD pathogenesis.

[1]  P. Salinas Wnt signaling in the vertebrate central nervous system: from axon guidance to synaptic function. , 2012, Cold Spring Harbor perspectives in biology.

[2]  Lei Chen,et al.  Inferring Novel Tumor Suppressor Genes with a Protein-Protein Interaction Network and Network Diffusion Algorithms , 2018, Molecular therapy. Methods & clinical development.

[3]  Lei Chen,et al.  Predicting Drug Side Effects with Compact Integration of Heterogeneous Networks , 2019 .

[4]  Tao Liu,et al.  Inferring anatomical therapeutic chemical (ATC) class of drugs using shortest path and random walk with restart algorithms. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[5]  Damian Szklarczyk,et al.  STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets , 2018, Nucleic Acids Res..

[6]  P. Robinson,et al.  Walking the interactome for prioritization of candidate disease genes. , 2008, American journal of human genetics.

[7]  John G. Collard,et al.  Rac1 and Rac3 have opposing functions in cell adhesion and differentiation of neuronal cells , 2007, Journal of Cell Science.

[8]  G. Esposito,et al.  A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder , 2018, Front. Mol. Neurosci..

[9]  Lei Chen,et al.  iATC-NRAKEL: an efficient multi-label classifier for recognizing anatomical therapeutic chemical classes of drugs , 2019, Bioinform..

[10]  Lei Chen,et al.  Prediction of Drug Side Effects with a Refined Negative Sample Selection Strategy , 2020, Comput. Math. Methods Medicine.

[11]  H. Monyer,et al.  Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour , 2014, Molecular Psychiatry.

[12]  T. Kemper,et al.  Parvalbumin‐, calbindin‐, and calretinin‐immunoreactive hippocampal interneuron density in autism , 2010, Acta neurologica Scandinavica.

[13]  Chi-Chung Hui,et al.  Disruption at the Ptchd1 Locus on Xp22.11 in Autism Spectrum Disorder and Intellectual Disability Nih Public Access , 2010 .

[14]  Minyi Xu,et al.  Sex Hormones in Autism: Androgens and Estrogens Differentially and Reciprocally Regulate RORA, a Novel Candidate Gene for Autism , 2011, PloS one.

[15]  K. Khalili,et al.  Developmental Expression of Wnt Signaling Factors in Mouse Brain , 2002, Cancer biology & therapy.

[16]  A. Kolevzon,et al.  Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency , 2013, Molecular Autism.

[17]  T. Furuichi,et al.  Developmentally Regulated Ca2+-Dependent Activator Protein for Secretion 2 (CAPS2) is Involved in BDNF Secretion and is Associated with Autism Susceptibility , 2009, The Cerebellum.

[18]  Brian K. Lee,et al.  The Changing Epidemiology of Autism Spectrum Disorders. , 2017, Annual review of public health.

[19]  A. Routtenberg,et al.  Neuron-specific protein F1/GAP-43 shows substrate specificity for the beta subtype of protein kinase C. , 1990, Biochemical and biophysical research communications.

[20]  Eric M. Morrow,et al.  Autism and Brain Development , 2008, Cell.

[21]  Jane E. Roberts,et al.  Early identification of autism in fragile X syndrome: a review. , 2013, Journal of intellectual disability research : JIDR.

[22]  Wei Hsu,et al.  Gpr177/mouse Wntless is essential for Wnt‐mediated craniofacial and brain development , 2011, Developmental dynamics : an official publication of the American Association of Anatomists.

[23]  Matthew W. Mosconi,et al.  Consensus Paper: Pathological Role of the Cerebellum in Autism , 2012, The Cerebellum.

[24]  D. Pandya,et al.  Motor projections to the basis pontis in rhesus monkey , 2004, The Journal of comparative neurology.

[25]  D. Storm,et al.  Overexpression of the Type 1 Adenylyl Cyclase in the Forebrain Leads to Deficits of Behavioral Inhibition , 2015, The Journal of Neuroscience.

[26]  Shuaiqun Wang,et al.  Drug target group prediction with multiple drug networks. , 2020, Combinatorial chemistry & high throughput screening.

[27]  G. Ciceri,et al.  Essential role of Rac1 and Rac3 GTPases in neuronal development , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Xiangtian Yu,et al.  Integrative enrichment analysis: a new computational method to detect dysregulated pathways in heterogeneous samples , 2015, BMC Genomics.

[29]  T Pawson,et al.  Unified Nomenclature for Eph Family Receptors and Their Ligands, the Ephrins , 1997, Cell.

[30]  A. Chauhan,et al.  Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities , 2012, International journal of biological sciences.

[31]  I. Miko,et al.  Eph-ephrin signaling in nervous system development , 2016, F1000Research.

[32]  Lei Wang,et al.  A Novel Approach based on Bipartite Network to Predict Human Microbe-Disease Associations , 2017 .

[33]  Lei Wang,et al.  A Novel Model for Predicting LncRNA-disease Associations based on the LncRNA-MiRNA-Disease Interactive Network , 2019, Current Bioinformatics.

[34]  K. Kaestner,et al.  KLF Family Members Regulate Intrinsic Axon Regeneration Ability , 2009, Science.

[35]  G. Dawson,et al.  Brief Report: Biochemical Correlates of Clinical Impairment in High Functioning Autism and Asperger’s Disorder , 2009, Journal of autism and developmental disorders.

[36]  Sharmila Banerjee-Basu,et al.  AutDB: a platform to decode the genetic architecture of autism , 2017, Nucleic Acids Res..

[37]  M. Baudry,et al.  Calpain-2-Mediated PTEN Degradation Contributes to BDNF-Induced Stimulation of Dendritic Protein Synthesis , 2013, The Journal of Neuroscience.

[38]  Michael E. Greenberg,et al.  Activity-dependent neuronal signalling and autism spectrum disorder , 2013, Nature.

[39]  S. Scherer,et al.  Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. , 2013, American journal of human genetics.

[40]  A. Spasov,et al.  [Neural network modeling of multitarget RAGE inhibitory activity]. , 2019, Biomeditsinskaia khimiia.

[41]  A. Sheikh,et al.  Up-regulation of Ras/Raf/ERK1/2 signaling impairs cultured neuronal cell migration, neurogenesis, synapse formation, and dendritic spine development , 2012, Brain Structure and Function.

[42]  H. Kalkman A review of the evidence for the canonical Wnt pathway in autism spectrum disorders , 2012, Molecular Autism.

[43]  Karl J. Friston,et al.  Neuroscience and Biobehavioral Reviews , 2014 .

[44]  Richard E Thompson,et al.  Autism spectrum disorder in fragile X syndrome: A longitudinal evaluation , 2009, American journal of medical genetics. Part A.

[45]  N. Srivastava,et al.  In-Silico Identification of Drug Lead Molecule Against Pesticide Exposed-neurodevelopmental Disorders Through Network-Based Computational Model Approach , 2019, Current Bioinformatics.

[46]  M. Noda,et al.  Exploring the Multifactorial Nature of Autism Through Computational Systems Biology: Calcium and the Rho GTPase RAC1 Under the Spotlight , 2013, NeuroMolecular Medicine.

[47]  Christian Wehrle,et al.  Wnt3a plays a major role in the segmentation clock controlling somitogenesis. , 2003, Developmental cell.

[48]  H. John Calretinin : A Gene for a Novel Calcium-binding Protein Expressed Principally in Neurons , 2003 .

[49]  Yu-Dong Cai,et al.  A computational method using the random walk with restart algorithm for identifying novel epigenetic factors , 2018, Molecular Genetics and Genomics.

[50]  V. Napolioni,et al.  Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes , 2011, European Journal of Human Genetics.

[51]  R. Dallel,et al.  Glycine Inhibitory Dysfunction Turns Touch into Pain through PKCgamma Interneurons , 2007, PloS one.