Human Gene最新文献

{"title":"Role of GSTP1 functional polymorphisms in molecular pathogenesis of colorectal cancer","authors":"Sravanthi Malempati ,&nbsp;Neelam Agrawal ,&nbsp;Devalaraju Ravisankar ,&nbsp;Venkata Sai Rahul Trivedi Kothapalli ,&nbsp;Srinivasulu Cheemanapalli ,&nbsp;Raghava Rao Tamanam ,&nbsp;Suresh Govatati ,&nbsp;Pasupuleti Sreenivasa Rao","doi":"10.1016/j.humgen.2024.201335","DOIUrl":"10.1016/j.humgen.2024.201335","url":null,"abstract":"<div><p>Glutathione S-transferase P1 (GSTP1) plays a crucial role in the detoxification of harmful substances and cancer-causing agents. Single nucleotide polymorphisms (SNPs) in GSTP1 can affect its ability to catalyze reactions and detoxify, thereby influencing the risk of developing colorectal cancer (CRC). This study aimed to investigate the impact of functional SNPs (fSNPs) in GSTP1 on the risk of CRC, as well as their structural and functional consequences. We analyzed a total of 126 selected GSTP1 SNPs, including fSNPs <em>rs1695 A &gt; G</em> (I105V) and <em>rs1138272 C &gt; T</em> (A114V), in CRC patients (<em>n</em> = 103) and controls (<em>n</em> = 107) of south Indian origin using PCR-sequencing analysis with genomic DNA from blood samples. To assess the structural integrity of <em>GSTP1</em> fSNPs, we conducted in silico analysis using various tools such as Swiss PDB Viewer, pyMOL mutagenesis wizard, ProSA-Web, and Pdbsum. Additionally, we performed functional characterization of <em>GSTP1</em> fSNPs using cell and molecular biology techniques. Our findings revealed a significant association between the I105V fSNP and CRC risk, while the A114V fSNP did not show any significance. However, both fSNPs exhibited stronger linkage disequilibrium in patients compared to controls. In silico analysis indicated a loss of structural integrity and reduced electrostatic potential energy in the double mutant <em>GSTP1</em> (V105/V114) compared to the native (I105/A114) or single mutant (V105/A114 and I105/V114) forms. Furthermore, FHC cells transfected with the <em>GSTP1</em> I105V variant exhibited increased proliferation, invasion, and colony formation, along with decreased GST activity compared to carriers of the wild-type <em>GSTP1</em>. On the other hand, the <em>GSTP1</em> A114V variant did not show a significant effect. Interestingly, FHC cells transfected with the double mutant <em>GSTP1</em> variant (V105/V114) demonstrated synergistic and enhanced effects compared to the <em>GSTP1</em> I105V variant. Consistent with these findings, plasma GST activity was significantly lower in haplogroups carrying both fSNPs compared to haplogroups with single or no fSNPs. To summarize, our findings indicate that while <em>GSTP1</em> I105V alone contributes to the etiology of CRC, A114V does not; however, their combined presence has a more significant impact.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201335"},"PeriodicalIF":0.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of family dynamics on cancer progression and patient outcomes: An analysis of emotional and psychological support","authors":"Hashim Talib Hashim ,&nbsp;Ali Talib Hashim ,&nbsp;Ali Mahdi Mansour ,&nbsp;Hossam Tharwat Ali ,&nbsp;Narjiss Aji ,&nbsp;Maryam Chichah ,&nbsp;Mrinmoy Kundu ,&nbsp;Amasee Falah Jabbar","doi":"10.1016/j.humgen.2024.201339","DOIUrl":"10.1016/j.humgen.2024.201339","url":null,"abstract":"<div><h3>Background</h3><p>Cancer is a group of diseases that results from the growth of cells in an uncontrolled way, and in addition spreading of abnormal cells. At the molecular level, Alterations of oncogenes, tumor-suppresser genes, and microRNA genes cause cancer. These alterations of genes usually occur at the somatic level, if they occur as germline mutations, they can cause heritable or familial cancer.</p></div><div><h3>Materials/methods</h3><p>This is a cross-sectional study which aims to find if there is any relationship between genetic relationship (genes) and cancer development, symptoms severity and prognosis. This study was conducted during the period of January 2022 and August 2022, and consisted of 1998 participants.</p></div><div><h3>Results</h3><p>There was a statistical difference in the distribution of participants' relative symptoms severity and improvement based on the duration they stayed with those people. Staying for days followed by weeks was the most reported in the group of participants with the same symptoms' severity of the diseased relative. On the opposite side, a longer duration of years was the predominant for worse symptoms of the family members despite the improvement of the patient.</p></div><div><h3>Conclusions</h3><p>Family history of cancer has been used by epidemiologists as a proxy for a genetically determined predisposition. However, a shared environment and similar lifestyles can also lead to multiple cancers in the same family. Genes' communication has a role in spreading the cancer among families.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201339"},"PeriodicalIF":0.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum oxidative stressors levels and association of mtDNA variants with type 2 diabetes mellitus in the Central India population","authors":"Tejas Tajane ,&nbsp;Prafulla Ambulkar ,&nbsp;Pranita Waghmare ,&nbsp;Bharati Taksande ,&nbsp;Jwalant Waghmare","doi":"10.1016/j.humgen.2024.201337","DOIUrl":"10.1016/j.humgen.2024.201337","url":null,"abstract":"<div><h3>Background</h3><p>The mitochondrial genome has a high rate of mutability which plays a major role in pathogenic mutations. These mutations are implicated with mitochondrial dysfunction increasing the vulnerability to Diabetes Mellitus (DM).</p></div><div><h3>Aim</h3><p>The study aimed to evaluate the changes in oxidative markers and analyse the specific mitochondrial DNA variants that contributed to DM in the central Indian population.</p></div><div><h3>Method</h3><p>To assess mitogenomic alteration, Sanger sequencing was used to identify the single nucleotide polymorphisms (SNPs) or variants, while ELISA kits were used to evaluate oxidative stress.</p></div><div><h3>Results</h3><p>The levels of 8-Hydroxy-2-deoxyguanosine (8-OHdG) and Malondialdehyde (MDA) in type 2 diabetes mellitus (T2DM) were significantly higher than in healthy individual (HI). In T2DM (3371.80 ± 1110.7 pg/ml) the levels of 8-OHdG were significantly greater and were found to be nine times higher compared to the control group (<em>P</em> &lt; 0.001). Additionally, MDA level which is indicative of lipid peroxidation, in the diabetic groups (39.34 ± 23.05 ng/ml) contributed to 18 times higher than the control groups (2.16 ± 2 ng/ml). Moreover, 52 variants were found in our population, among which C10400T variants were significantly prevalent and clustered with the A10398G. These variants confirmed a strong association, on analysis for linkage disequilibrium (r²), with a slightly higher r² value in the T2DM group (0.92) compared to controls (0.85), indicating a stronger link with diabetes. According to multivariate regression analysis, variants associated with the mitogenome such as C16192T (CI: 0.004 to 1.30, <em>p</em> = 0.028) were found to play a protective role against T2DM. Furthermore, A3384G and G16129A may contribute to the protective role against the risk of developing diabetes.</p></div><div><h3>Conclusion</h3><p>The study demonstrates that diabetic patients are more vulnerable to certain mtDNA variants, directly linked to increased hyperglycemia. Elevated free radical-mediated oxidative stress likely affects these mtDNA variants.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201337"},"PeriodicalIF":0.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minning of Immuno-mitotic and GABAergic genes as potential biomarkers of glioblastoma: An integrated transcriptomic analysis","authors":"Naureen Mallick,&nbsp;Reaz Uddin","doi":"10.1016/j.humgen.2024.201336","DOIUrl":"10.1016/j.humgen.2024.201336","url":null,"abstract":"<div><p>Glioblastoma (GBM) is a highly lethal Central Nervous System (CNS) tumor prevalent in both adults and children, exhibiting elevated rates of mortality and morbidity. Due to the heterogenous nature of GBM, coupled with its nonspecific symptoms underscore the imperative for innovative biomarkers to enhance prognosis and the development of efficacious therapeutic interventions. This bioinformatics study seeks to elucidate the culprit genes, both up-regulated and down-regulated, within the context of their functional relevance, through a comparative analysis of gene expression profiles in GBM and normal brain tissues. Deregulated genes were identified from two Gene Expression Omnibus (GEO) datasets, employing the GEO2R tool to analyze expression data from normal and GBM tissues. Subsequently, differences in expression of genes (DEGs) through functional enrichment analysis were conducted by DAVID to discern their functional implications. Further, Protein-Protein Interaction (PPI) networks were constructed to identify hub genes among the selected up-regulated and down-regulated genes, employing various bioinformatics tools. The impact of the selected hub genes on patient overall survival was investigated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Notably, the up-regulated hub genes KIF2C and TTK exhibited significant correlations with overall survival, implicating their potential as immuno-mitotic biomarkers. Conversely, GAD2, the sole down-regulated hub gene, emerged as a promising molecular target for GBM, given its association with GABAergic signaling and amino acid metabolism. Consequently, these findings suggest that KIF2C and TTK may serve as immune-mitotic biomarkers, while GAD2 could be explored as a molecular target for GBM therapy. Nevertheless, additional research is essential to unravel the precise mechanistic underpinnings of GBM.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201336"},"PeriodicalIF":0.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid biopsy in brain tumors: Potential for impactful clinical applications","authors":"Tania Eid ,&nbsp;Lina Ghandour ,&nbsp;Joseph Abi Ghanem ,&nbsp;Hazem Assi ,&nbsp;Rami Mahfouz","doi":"10.1016/j.humgen.2024.201333","DOIUrl":"10.1016/j.humgen.2024.201333","url":null,"abstract":"<div><p>Despite the improvements in diagnostic and therapeutic techniques, heterogeneous constitution and non-invasive diagnosis remain major clinical challenges for brain tumors. In such a context, liquid biopsy is a noninvasive method that analyses tumor-derived biomarkers in body fluids and thus appears quite promising. This review explores the potential for circulating tumor cells, circulating tumor DNA, microRNAs, proteins, and exosomes as liquid biopsy markers in brain tumors. Although such biomarkers have potential for early detection, monitoring of disease progression, and guiding therapy, the limitations in the form of low levels of biomarkers and analytical complexities persist. Artificial intelligence integrated with liquid biopsy can therefore be expected to improve diagnostic accuracy and clinical utility. Further research, standardization, and clinical validation are needed to exploit the full potential of liquid biopsy in brain tumor management.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201333"},"PeriodicalIF":0.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773044124000779/pdfft?md5=a38488b52d1ae0ec4f9454b7d9fb5e75&pid=1-s2.0-S2773044124000779-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of mutational features of colorectal cancer and multiple primary cancers including colorectal component: Data from the Cancer Genome Atlas","authors":"Nataliya N. Timoshkina,&nbsp;Dmitry Yu Gvaldin,&nbsp;Moez Eid,&nbsp;Dema Alset,&nbsp;Nataliya A. Petrusenko,&nbsp;Inna A. Novikova,&nbsp;Oleg I. Kit","doi":"10.1016/j.humgen.2024.201334","DOIUrl":"10.1016/j.humgen.2024.201334","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is the second in mortality among cancers with high incidence worldwide. About 5 % of patients had a previous oncopathology and 20 % develop a second malignancy. CRC molecular genetic mechanisms in primary multiple cancers (MPCs) are not fully understood. This study aimed to investigate mutational characteristics of primary CRC compared to MPCs with colorectal component. 336 CRC patients and 52 MPCs patients with a colorectal component (C97CRC) (TCGA-COAD data) were included. Comparative bioinformatics analysis of genetic mutations, their interactions, effect on signaling pathways, survival rate, and druggable categories was conducted. CRC was characterized by <em>PIK3CA</em> and <em>APC</em> mutations, while 17 mutations in other genes were identified in C97CRC. In CRC group, co-occurring somatic variants in <em>TP53/APC</em> and <em>KRAS/APC</em> were the most common, while in C97CRC, <em>KRAS/SOX9</em> was specifically found. <em>TP53</em>/<em>SYNE1</em>, <em>TP53</em>/<em>MUC16</em>, and <em>TP53/TTN</em> mutational combinations were associated with a decreased survival rate in CRC group. Collagen type VI α3-chain protease and its inhibitor were suggested as specific druggable targets in C97CRC group. The differences in mutational profiles between groups may indicate evolutionary features of CRC as a primary and secondary malignancy. Described druggable categories open up prospects for treatment development of CRC and MPCs with a colorectal component.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201334"},"PeriodicalIF":0.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis of the effects of non-synonymous SNPs associated with human GSK3B gene on its structure and function","authors":"Mayank Kumar ,&nbsp;Ruchika Bharti ,&nbsp;Gajendra Kumar Azad","doi":"10.1016/j.humgen.2024.201332","DOIUrl":"10.1016/j.humgen.2024.201332","url":null,"abstract":"<div><p>Single Nucleotide Polymorphisms (SNPs) are abundantly identified by next generation sequencing (NGS) technology. Glycogen synthase kinase-3 beta (GSK3B), a widely expressed protein kinase, plays pivotal roles in cellular pathways. However, study on SNPs associated with GSK3B and their functional consequences is lacking. In this study, we analysed non-synonymous SNPs of GSK3B gene and their implications using computational tools. From NCBI dbSNP, 103,087 SNPs of GSK3B were initially gathered, later narrowed down to 255 unique nsSNPs. Around one-third of the nsSNPs resulted in charge and polarity change of the amino acids of the protein. 41 nsSNPs were found to significantly alter the stability of GSK3B protein (ΔΔG ≤ -1 or ≥ 1 kcal/mol) and few of them also affected the disorderness at the mutation site. Evolutionary conservation of the nsSNPs in the protein revealed 25 nsSNP may be deleterious to GSK3B protein function. Finally, 4 critical nsSNPs (Y161C, R167G, P225L and Y234D) were identified that can significantly alter both the stability and function of GSK3B. Furthermore, this study predicted 60 post-translational modification sites in GSK3B among which 26 sites contained nsSNPs. Interestingly, 7 upstream ORFs (uORFs) with high ribosomal occupancy were also detected in GSK3B mRNA that can reduce the expression of GSK3B protein. Altogether, this study has employed various in silico methods to characterize GSK3B nsSNPs, but they have limitations. These tools often overlook the cellular context, interacting partners, PTMs and the dynamic nature of proteins, which can affect protein behaviour and function. Despite these limitations, in silico tools are valuable for initial screening and prioritizing SNPs. The prioritized SNPs obtained in this study (Y161C, R167G, P225L and Y234D) should be experimentally validated using techniques like genome editing, biochemical assays, interactome analysis in cell lines and animal models to confirm their biological relevance.</p><p><strong>Clinical trial registration:</strong> Not Applicable.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201332"},"PeriodicalIF":0.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of TRIOBP and MYO15A variants in Iranian families with autosomal recessive non-syndromic hearing loss","authors":"Nasrin Azizi ,&nbsp;Hamid Reza Khorram Khorshid ,&nbsp;Kimia Kahrizi ,&nbsp;Niloofar Bazazzadegan ,&nbsp;Saeed Dorgaleleh ,&nbsp;Fateme Zahedi Abghari ,&nbsp;Narges Shahmohammad ,&nbsp;Reza Najafipour","doi":"10.1016/j.humgen.2024.201331","DOIUrl":"10.1016/j.humgen.2024.201331","url":null,"abstract":"<div><h3>Background</h3><p>Deafness is a prevalent sensory and neurological disorder that impacts over 466 million individuals globally. Congenital deafness is the most prevalent birth defect, occurring in approximately 2–3 out of every 1000 births. It is recognized as a highly diverse condition. &gt;50% of congenital deafness has genetic causes and the rest is due to environmental causes or both. With the development of next-generation sequencing and bioinformatics tools, whole-exome sequencing has been proposed as one of the effective methods for diagnosing genetics of hearing loss.</p></div><div><h3>Method</h3><p>Five Iranian Autosomal recessive non-syndromic hearing loss (ARNSHL) families negative for <em>GJB2</em> (NM_004004.6) gene mutations from Sistan and Baluchestan province were selected for further study by whole-exome sequencing analysis. The analysis procedure was performed using multiple bioinformatics tools and websites after filling the consent form and extracting DNA from whole blood using the salting out method. After detecting the variants in priority and confirming them in the probands by Sanger sequencing, other family members were studied to confirm the variant within the family.</p></div><div><h3>Results</h3><p>After analyzing the families recruited for this study, four known genes along with known and novel variants were discovered. Mutations found in the <em>MYO15A</em>, <em>SLC26A4</em>, <em>TRIOBP</em> and <em>TECTA</em> genes among which, the variants found in <em>TRIOBP</em> (NM_001039141.3, p.R283X) and <em>MYO15A</em> (NM_016239.4, p.P2880Rfs*19) were novel. Other known variants were <em>TECTA</em> (NM_005422.4, p.W1534X) and <em>SLC26A4</em> (NM_000441.2, p.V239D). No genes or variants that might contribute to hearing loss have been identified within one of the families.</p></div><div><h3>Conclusion</h3><p>Our study's findings support previous research that has identified <em>SLC26A4</em>, <em>MYO15A</em>, and <em>TECTA</em> genes as common genetic factors following <em>GJB2</em> in our population.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201331"},"PeriodicalIF":0.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valencene ameliorates ox-LDL induced foam cell formation by suppressing inflammation and modulating key proteins involved in the atherogenesis on THP-1 derived macrophages","authors":"Mahesh Chandran ,&nbsp;Abhirami ,&nbsp;Bincy Shareef ,&nbsp;Arun Surendran ,&nbsp;Abdul Jaleel ,&nbsp;Janeesh Plakkal Ayyappan","doi":"10.1016/j.humgen.2024.201330","DOIUrl":"10.1016/j.humgen.2024.201330","url":null,"abstract":"<div><p>Atherosclerosis is a distinct risk factor for cardiovascular and cerebrovascular disorders, which are significant contributors to global mortality. It is defined by macrophage-derived foam cell development followed by persistent inflammation, plaque formation, fibrosis and thrombosis. Studies have shown valencene, a sesquiterpene obtained from Valencia oranges, has several health-promoting properties. However, its protective effect against atherosclerosis and foam cell models remains unexplored. The present investigation revealed that valencene treatment suppresses foam cell generation and accumulation of lipids in THP-1-derived cells macrophage models activated with oxidized low-density lipoprotein (ox-LDL), maintained in vitro. The intracellular lipid content was qualitatively and semi-quantitatively analyzed by Oil Red O staining, and the compound's cytotoxicity was assessed through the MTT assay, considering both time-dependent and dose-dependent factors. The RT-qPCR results showed promising anti-inflammatory and anti-oxidant enzyme status upon valencene treatment. The H2DCFDA staining revealed valencene's ability to reduce the oxidative stress induced by ox-LDL. Further, high-throughput proteomic profiling was carried out to identify the target proteins affected by valencene treatment and thereby explore its mechanism of action on foam cell models. Proteomic studies revealed that valencene treatment regulates the expression of several proteins associated with ox-LDL-induced inflammation, defective cholesterol homeostasis and cholesterol efflux pathways.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201330"},"PeriodicalIF":0.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of overlapping molecular mechanisms in tuberculosis and sarcoidosis: A bioinformatics approach","authors":"Sanjukta Dasgupta,&nbsp;Sayantan Ghosh","doi":"10.1016/j.humgen.2024.201329","DOIUrl":"10.1016/j.humgen.2024.201329","url":null,"abstract":"<div><h3>Background</h3><p>Tuberculosis (TB) and sarcoidosis are chronic granulomatous diseases sharing similar symptoms, immune responses, and radiological characteristics. Transcriptome analysis offers insights into gene expression, regulation, and cellular processes, facilitating the understanding of shared molecular mechanisms.</p></div><div><h3>Methods</h3><p>Microarray datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) were analysed to identify differentially expressed genes (DEGs) in TB and sarcoidosis compared to controls. DEGs were identified using the GEO2R tool, and subsequent functional enrichment analysis was conducted using EnrichR. Protein-protein interaction (PPI) networks, as well as gene-miRNA and transcription factor-DEG interaction networks, were constructed. In addition, pathway analysis and molecular docking of target proteins were conducted to further elucidate the biological mechanisms involved in both diseases.</p></div><div><h3>Results</h3><p>Fifteen genes, including <em>ANKRD22, BATF2, DHRS9, EPSTI1, ETV7, FCGR1A, FCGR1B, GBP1, GBP5, SERPING1, NELL2, CCR7, PASK, LRRN3</em>, and <em>SLC16A10</em>, were commonly altered in TB and sarcoidosis as compared to controls. Gene network analysis revealed 48.89% co-expression and 26.10% physical interaction between these overlapping genes. PPI networks showed a total of 15 nodes and 28 edges present between the connected proteins (PPI enrichment <em>p</em>-value:&lt;1.0e−16). MiRNAs and transcription factors that exhibited the highest interaction with DEGs included hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-335-5p, and EPAS1, HIF1A, KLF2, respectively. Pathway analysis indicated enrichment of IFN gamma signaling in both diseases. Molecular docking revealed weighted scores of −884.4, −851.9, and − 637.1 between three key proteins (PASK-GBP1, PASK-GBP5, and GBP1-GBP5).</p></div><div><h3>Conclusion</h3><p>The shared dysregulated genes in TB and sarcoidosis demonstrate notable co-expression and physical interaction, constituting a PPI network enriched in the IFN-gamma signaling pathway.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201329"},"PeriodicalIF":0.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}