Single-Cell RNA Sequencing Technology Landscape in 2023.

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and the dynamics of gene expression, bearing profound significance in stem cell research. Depending on the starting materials used for analysis, scRNA-seq encompasses scRNA-seq and single-nucleus RNA sequencing (snRNA-seq). scRNA-seq excels in capturing cellular heterogeneity and characterizing rare cell populations within complex tissues, while snRNA-seq is advantageous in situations where intact cell dissociation is challenging or undesirable (eg, epigenomic studies). A number of scRNA-seq technologies have been developed as of late, including but not limited to droplet-based, plate-based, hydrogel-based, and spatial transcriptomics. The number of cells, sequencing depth, and sequencing length in scRNA-seq can vary across different studies. Addressing current technical challenges will drive the future of scRNA-seq, leading to more comprehensive and precise insights into cellular biology and disease mechanisms informing therapeutic interventions.

NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways.

BACKGROUND: Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology. METHODS: Trio-based whole exome sequencing was conducted on ASD families. Genome editing technique was used to knock out the candidate causal gene in a relevant cell line. ATAC-seq, ChIP-seq and RNA-seq were performed to investigate the functional impact of knockout (KO) or mutation in the candidate gene. RESULTS: We identified a novel candidate gene NASP (nuclear autoantigenic sperm protein) for epigenetic dysregulation in ASD in a Chinese nuclear family including one proband with autism and comorbid atopic disease. The de novo likely gene disruptive variant tNASP(Q289X) subjects the expression of tNASP to nonsense-mediated decay. tNASP KO increases chromatin accessibility, promotes the active promoter state of genes enriched in synaptic signalling and leads to upregulated expression of genes in the neural signalling and immune signalling pathways. Compared with wild-type tNASP, tNASP(Q289X) enhances chromatin accessibility of the genes with enriched expression in the brain. RNA-seq revealed that genes involved in neural and immune signalling are affected by the tNASP mutation, consistent with the phenotypic impact and molecular effects of nasp-1 mutations in Caenorhabditis elegans. Two additional patients with ASD were found carrying deletion or deleterious mutation in the NASP gene. CONCLUSION: We identified novel epigenetic mechanisms mediated by tNASP which may contribute to the pathogenesis of ASD and its immune comorbidity.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

BACKGROUND: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID). OBJECTIVES: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID. METHODS: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s). The interactions between the CLEC16A locus and its target genes were identified using circular chromosome conformation capture. The transcription factor complexes mediating the chromatin interactions were determined by proteomic approach. The molecular pathways regulated by the CLEC16A locus were examined by RNA-sequencing and reverse phase protein array. RESULTS: This study showed that the CLEC16A locus is an enhancer regulating expression of multiple target genes including a distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate the chromatin interactions in an allele-specific manner. Disruption of the CLEC16A locus affects the AKT signaling pathway, as well as the molecular response of CD4+ T cells to immune stimulation. CONCLUSIONS: Through multiomics and targeted experimental approaches, this study elucidated the underlying target genes and signaling pathways involved in the genetic association of CLEC16A with CVID, and highlighted plausible molecular targets for developing novel therapeutics.

rhFGF-21 accelerates corneal epithelial wound healing through the attenuation of oxidative stress and inflammatory mediators in diabetic mice.

Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.

Anti-selective Cyclopropanation of Nonconjugated Alkenes with Diverse Pronucleophiles via Directed Nucleopalladation.

A facile approach to obtaining densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of nonconjugated alkenes with readily available pronucleophiles and gives excellent yields and good anti-selectivity using I2 and TBHP as oxidants. Pronucleophiles bearing a diverse collection of electron-withdrawing groups, including -CN, -CO2R, -COR, -SO2Ph, -CONHR, and -NO2, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C atoms. DFT calculations and mechanistic experiments reveal that the major mechanistic pathway involves the initial α-iodination of the nucleophile, followed by anti-carbopalladation and intramolecular C(sp3)-I oxidative addition. Strain-release-promoted C(sp3)-C(sp3) reductive elimination then furnishes the cyclopropanated product.

Mutation burden analysis of six common mental disorders in African Americans by whole genome sequencing.

Mental disorders present a global health concern and have limited treatment options. In today's medical practice, medications such as antidepressants are prescribed not only for depression but also for conditions such as anxiety and attention deficit hyperactivity disorder (ADHD). Therefore, identifying gene targets for specific disorders is important and offers improved precision. In this study, we performed a genetic analysis of six common mental disorders-ADHD, anxiety, depression, delays in mental development, intellectual disabilities (IDs) and speech/language disorder-in the ethnic minority of African Americans (AAs) using whole genome sequencing (WGS). WGS data were generated from blood-derived DNA from 4178 AA individuals, including 1384 patients with the diagnosis of at least one mental disorder. Mutation burden analysis was applied based on rare and deleterious mutations in the AA population between cases and controls, and further analyzed in the context of patients with single mental disorder diagnosis. Certain genes uncovered demonstrated significant P-values in mutation burden analysis. In addition, exclusive recurrences in specific type of disorder were scanned through gene-drug interaction databases to assess for availability of potential medications. We uncovered 15 genes harboring deleterious mutations, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) and Uronyl 2-Sulfotransferase (UST) for ADHD; Farnesyltransferase, CAAX Box, Beta (FNTB) for anxiety; Xin Actin Binding Repeat Containing 2 (XIRP2), Natriuretic Peptide C (NPPC), Serine/Threonine Kinase 33 (STK33), Pannexin 1 (PANX1) and Neurotensin (NTS) for depression; RUNX Family Transcription Factor 3 (RUNX3), Tachykinin Receptor 1 (TACR1) and NADH:Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) for delays in mental development; Hepsin (HPN) for ID and Collagen Type VI Alpha 3 Chain (COL6A3), Damage Specific DNA Binding Protein 1 (DDB1) and NADH:Ubiquinone Oxidoreductase Subunit A11 (NDUFA11) for speech/language disorder. Taken together, we have established critical insights into the development of new precision medicine approaches for mental disorders in AAs.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders.

The co-occurrence and familial clustering of neurodevelopmental disorders and immune disorders suggest shared genetic risk factors. Based on genome-wide association summary statistics from five neurodevelopmental disorders and four immune disorders, we conducted genome-wide, local genetic correlation and polygenic overlap analysis. We further performed a cross-trait GWAS meta-analysis. Pleotropic loci shared between the two categories of diseases were mapped to candidate genes using multiple algorithms and approaches. Significant genetic correlations were observed between neurodevelopmental disorders and immune disorders, including both positive and negative correlations. Neurodevelopmental disorders exhibited higher polygenicity compared to immune disorders. Around 50%-90% of genetic variants of the immune disorders were shared with neurodevelopmental disorders. The cross-trait meta-analysis revealed 154 genome-wide significant loci, including 8 novel pleiotropic loci. Significant associations were observed for 30 loci with both types of diseases. Pathway analysis on the candidate genes at these loci revealed common pathways shared by the two types of diseases, including neural signaling, inflammatory response, and PI3K-Akt signaling pathway. In addition, 26 of the 30 lead SNPs were associated with blood cell traits. Neurodevelopmental disorders exhibit complex polygenic architecture, with a subset of individuals being at a heightened genetic risk for both neurodevelopmental and immune disorders. The identification of pleiotropic loci has important implications for exploring opportunities for drug repurposing, enabling more accurate patient stratification, and advancing genomics-informed precision in the medical field of neurodevelopmental disorders.

Tf2O-Mediated P(O)-N Bond Formation of Either P(O)-OH or P(O)-H Reagents with Multitype Amines.

We have developed a Tf2O-mediated approach for the direct amination of either P(O)-OH or P(O)-H reagents with a variety of aliphatic or aromatic amines. Without the requirement of precious metals and toxic reagents, this protocol provides an alternative route to various phosphinamides and phosphoramides. The reaction proceeds under simple and mild conditions and can be effectively scaled up with similar efficiency.

UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

Otilonium bromide ameliorates pulmonary fibrosis in mice through activating phosphatase PPM1A.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

The experience of shared decision-making for people with asthma: A systematic review and metasynthesis of qualitative studies.

OBJECTIVES: To identify, describe and synthesise the views and experiences of adults living with asthma regarding shared decision-making (SDM) in the existing qualitative literature METHODS: We conducted a comprehensive search of 10 databases (list databases) from inception until September 2023. Screening was performed according to inclusion criteria. Tools from the Joanna Briggs lnstitute were utilised for the purposes of data extraction and synthesis in this study. The data extraction process in this study employed the Capability, Opportunity and Motivation Model of Behaviour (COM-B model) as a framework, and a pragmatic meta-aggregative approach was employed to synthesise the collected results. RESULTS: Nineteen studies were included in the metasynthesis. Three synthesised themes were identified: the capability of people living with asthma, the opportunities of people living with asthma in SDM, and the motivation of the people living with asthma in SDM. CONCLUSIONS: We have identified specific factors influencing people living with asthma engaging in SDM. The findings of this study can serve as a basis for the implementation of SDM in people living with asthma and provide insights for the development of their SDM training programs. The ConQual score for the synthesised findings was rated as low. To enhance confidence, future studies should address dependability and credibility factors. PRACTICE IMPLICATIONS: This review contemplates the implementation of SDM from the perspective of people living with asthma, with the aim of providing patient-centred services for them. The results of this review can benefit the implementation of SDM and facilitate information sharing. It offers guidance for SDM skills training among adults living with asthma, fosters a better doctor-patient relationship and facilitates consensus in treatment decisions, thereby enabling personalised and tailored medical care. PATIENT OR PUBLIC CONTRIBUTION: Three nursing graduate students participated in the data extraction and integration process, with two students having extensive clinical experience that provided valuable insights for the integration.

HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria.

GTPase high frequency of lysogenization X (HflX) is highly conserved in prokaryotes and acts as a ribosome-splitting factor as part of the heat shock response in Escherichia coli. Here we report that HflX produced by slow-growing Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a GTPase that plays a critical role in the pathogen's transition to a nonreplicating, drug-tolerant state in response to hypoxia. Indeed, HflX-deficient M. bovis BCG (KO) replicated markedly faster in the microaerophilic phase of a hypoxia model that resulted in premature entry into dormancy. The KO mutant displayed hallmarks of nonreplicating mycobacteria, including phenotypic drug resistance, altered morphology, low intracellular ATP levels, and overexpression of Dormancy (Dos) regulon proteins. Mice nasally infected with HflX KO mutant displayed increased bacterial burden in the lungs, spleen, and lymph nodes during the chronic phase of infection, consistent with the higher replication rate observed in vitro in microaerophilic conditions. Unlike fast growing mycobacteria, M. bovis BCG HlfX was not involved in antibiotic resistance under aerobic growth. Proteomics, pull-down, and ribo-sequencing approaches supported that mycobacterial HflX is a ribosome-binding protein that controls translational activity of the cell. With HflX fully conserved between M. bovis BCG and M. tuberculosis, our work provides further insights into the molecular mechanisms deployed by pathogenic mycobacteria to adapt to their hypoxic microenvironment.

Can orange colour facilitate the processing of happiness? An exploration study on happiness metaphor.

Colour is a ubiquitous perceptual stimulus, and theoretical models of colour and psychological functioning posit that colour plays a key role in influencing the behaviour and mental function of a person. One investigation and two experiments investigated the colour metaphor representation of happiness concepts and the mapping mode of the colour metaphor of happiness concepts. A questionnaire was conducted to explore the relationship between colour preference and happiness. Study 2 shows that the identification of happiness words was facilitated more when words were viewed on an orange background than when viewed on a blue background. Study 3 further verifies the links of the connection between colour and happiness at the sentence level, and the orange-happiness facilitation effect was replicated. These results document a novel influence of colour on emotion recognition processes, where an orange background may facilitate the processing of the concept of happiness and provide support for conceptual metaphor theory and colour-in-context theory.

Phenotyping of Methicillin-Resistant Staphylococcus aureus Using a Ratiometric Sensor Array.

Chemical tools capable of classifying multidrug-resistant bacteria (superbugs) can facilitate early-stage disease diagnosis and help guide precision therapy. Here, we report a sensor array that permits the facile phenotyping of methicillin-resistant Staphylococcus aureus (MRSA), a clinically common superbug. The array consists of a panel of eight separate ratiometric fluorescent probes that provide characteristic vibration-induced emission (VIE) profiles. These probes bear a pair of quaternary ammonium salts in different substitution positions around a known VIEgen core. The differences in the substituents result in varying interactions with the negatively charged cell walls of bacteria. This, in turn, dictates the molecular conformation of the probes and affects their blue-to-red fluorescence intensity ratios (ratiometric changes). Within the sensor array, the differences in the ratiometric changes for the probes result in "fingerprints" for MRSA of different genotypes. This allows them to be identified using principal component analysis (PCA) without the need for cell lysis and nucleic acid isolation. The results obtained with the present sensor array agree well with those obtained using polymerase chain reaction (PCR) analysis.

Redox-Paired Alkene Difunctionalization Enables Skeletally Divergent Synthesis.

Multistep organic synthesis enables conversion of simple chemical feedstocks into a more structurally complex product that serves a particular function. The target compound is forged over several steps, with concomitant generation of byproducts in each step to account for underlying mechanistic features of the reactions (e.g., redox processes). To map structure-function relationships, libraries of molecules are often needed, and these are typically prepared by iterating an established multistep synthetic sequence. An underdeveloped approach is designing organic reactions that generate multiple valuable products with different carbogenic skeletons in a single synthetic operation. Taking inspiration from paired electrosynthesis processes that are widely used in commodity chemical production (e.g., conversion of glucose to sorbitol and gluconic acid), we report a palladium-catalyzed reaction that converts a single alkene starting material into two skeletally distinct products in a single operation through a series of carbon-carbon and carbon-heteroatom bond-forming events enabled by mutual oxidation and reduction, a process that we term redox-paired alkene difunctionalization. We demonstrate the scope of the method in enabling simultaneous access to reductively 1,2-diarylated and oxidatively [3 + 2]-annulated products, and we explore the mechanistic details of this unique catalytic system using a combination of experimental techniques and density functional theory (DFT). The results described herein establish a distinct approach to small-molecule library synthesis that can increase the rate of compound production. Furthermore, these findings demonstrate how a single transition-metal catalyst can mediate a sophisticated redox-paired process through multiple pathway-selective events along the catalytic cycle.

Genomic variants exclusively identified in children with birth defects and concurrent malignant tumors predispose to cancer development.

Children with birth defects (BD) express distinct clinical features that often have various medical consequences, one of which is predisposition to the development of cancers. Identification of the underlying genetic mechanisms related to the development of cancer in BD patients would allow for preventive measures. We performed a whole genome sequencing (WGS) study on blood-derived DNA samples from 1566 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumors, 767 cancer-free BD probands, and 345 healthy individuals. Exclusive recurrent variants were identified in BD-cancer and BD-only patients and mapped to their corresponding genomic regions. We observed statistically significant overlaps for protein-coding/ncRNA with exclusive variants in exons, introns, ncRNAs, and 3'UTR regions. Exclusive exonic variants, especially synonymous variants, tend to occur in prior exons locus in BD-cancer children. Intronic variants close to splicing site (< 500 bp from exon) have little overlaps in BD-cancer and BD-only patients. Exonic variants in non-coding RNA (ncRNA) tend to occur in different ncRNAs exons regardless of the overlaps. Notably, genes with 5' UTR variants are almost mutually exclusive between the two phenotypes. In conclusion, we conducted the first genomic study to explore the impact of recurrent variants exclusive to the two distinguished clinical phenotypes under study, BD with or without cancer, demonstrating enrichment of selective protein-coding/ncRNAs differentially expressed between these two phenotypes, suggesting that selective genetic factors may underlie the molecular processes of pediatric cancer development in BD children.

Identification and characterization of inhibitors covalently modifying catalytic cysteine of UBE2T and blocking ubiquitin transfer.

UBE2T is an E2 ubiquitin ligase critical for ubiquitination of substrate and plays important roles in many diseases. Despite the important function, UBE2T is considered as an undruggable target due to lack of a pocket for binding to small molecules with satisfied properties for clinical applications. To develop potent and specific UBE2T inhibitors, we adopted a high-throughput screening assay and two compounds-ETC-6152 and ETC-9004 containing a sulfone tetrazole scaffold were identified. Solution NMR study demonstrated the direct interactions between UBE2T and compounds in solution. Further co-crystal structures reveal the binding modes of these compounds. Both compound hydrolysation and formation of a hydrogen bond with the thiol group of the catalytic cysteine were observed. The formation of covalent complex was confirmed with mass spectrometry. As these two compounds inhibit ubiquitin transfer, our study provides a strategy to develop potent inhibitors of UBE2T.

Type H vessels-a bridge connecting subchondral bone remodelling and articular cartilage degeneration in osteoarthritis development.

Recent studies have shed light on the cellular and molecular mechanisms that link subchondral bone remodelling and angiogenesis in knee osteoarthritis (OA). Type H vessels are a newly identified bone blood vessel characterized by high expression of CD31 and endomucin that are coupled with osteogenesis. Factors including mechanical loading, TGF-ß1, platelet-derived growth factor type BB, the osteoprotegerin-RANK ligand-RANK system, osteopontin, mechanistic target of rapamycin, VEGF, stromal cell-derived factor l and prostaglandin E2 participate in the formation of type H vessels in osteoarthritic subchondral bone. In this review, we summarize the current understanding of type H vessels in knee OA, as well as the signalling pathways involved and potential therapeutic medicines. In future, the pathogenesis of knee OA could be further clarified by connecting type H vessels and the design of new disease-modifying osteoarthritis drugs. However, further experiments are needed to determine the upstream signals regulating type H vessel formation in osteoarthritic subchondral bone.

Application of deep learning algorithm on whole genome sequencing data uncovers structural variants associated with multiple mental disorders in African American patients.

Mental disorders present a global health concern, while the diagnosis of mental disorders can be challenging. The diagnosis is even harder for patients who have more than one type of mental disorder, especially for young toddlers who are not able to complete questionnaires or standardized rating scales for diagnosis. In the past decade, multiple genomic association signals have been reported for mental disorders, some of which present attractive drug targets. Concurrently, machine learning algorithms, especially deep learning algorithms, have been successful in the diagnosis and/or labeling of complex diseases, such as attention deficit hyperactivity disorder (ADHD) or cancer. In this study, we focused on eight common mental disorders, including ADHD, depression, anxiety, autism, intellectual disabilities, speech/language disorder, delays in developments, and oppositional defiant disorder in the ethnic minority of African Americans. Blood-derived whole genome sequencing data from 4179 individuals were generated, including 1384 patients with the diagnosis of at least one mental disorder. The burden of genomic variants in coding/non-coding regions was applied as feature vectors in the deep learning algorithm. Our model showed ~65% accuracy in differentiating patients from controls. Ability to label patients with multiple disorders was similarly successful, with a hamming loss score less than 0.3, while exact diagnostic matches are around 10%. Genes in genomic regions with the highest weights showed enrichment of biological pathways involved in immune responses, antigen/nucleic acid binding, chemokine signaling pathway, and G-protein receptor activities. A noticeable fact is that variants in non-coding regions (e.g., ncRNA, intronic, and intergenic) performed equally well as variants in coding regions; however, unlike coding region variants, variants in non-coding regions do not express genomic hotspots whereas they carry much more narrow standard deviations, indicating they probably serve as alternative markers.