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Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

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Big Data Mining and Analytics 2024年第1期7卷 107-130页

作者： Nadezhda Yu.Biziukova Sergey M.Ivanov Oga A.Tarasova Department of bioinformatics Institute of Biomedical ChemistryMoscow 119121Russia Department of bioinformatics Pirogov Russian National Research Medical UniversityMoscow 117997Russia

Analysis of molecular mechanisms that lead to the development of various types of tumors is essential for biology and medicine,because it may help to find new therapeutic opportunities for cancer treatment and cure including personalized treatment *** of the pathways known to be important for the development of neoplastic diseases and pathological processes is the Hedgehog signaling pathway that normally controls human embryonic *** accumulation of various types of biological data,including interactions between proteins,regulation of genes transcription,proteomics,and metabolomics experiments results,allows the application of computational analysis of these big data for identification of key molecular mechanisms of certain diseases and pathologies and promising therapeutic *** aim of this study is to develop a computational approach for revealing associations between human proteins and genes interacting with the Hedgehog pathway components,as well as for identifying their roles in the development of various types of *** automatically collect sets of abstract texts from the NCBI PubMed bibliographic *** recognition of the Hedgehog pathway proteins and genes and neoplastic diseases we use a dictionary-based named entity recognition approach,while for all other proteins and genes machine learning method is *** association extraction,we develop a set of semantic *** complete the results of the text analysis with the gene set enrichment *** identified key pathways that may influence the Hedgehog pathway and their roles in tumor development are then verified using the information in the literature.

关键词： text-mining data mining Hedgehog pathway neoplastic processes enrichment analysis pathology molecularmechanisms

Genome-wide DNA methylome analysis reveals a critical role of methylation-dysregulated lncRNAs in autophagy regulation in glioblastoma

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Genes & Diseases 2024年第5期11卷 51-54页

作者： Hongying Zhao Ying Liu Meiting Fei Lin Bo Lixia Wang Yaopeng Shu Peiqi Ben Li Wang College of bioinformatics Science and Technology Harbin Medical UniversityHarbinHeilongjiang 150081China

Glioblastoma(GBM)is the most common primary malignant intracranial tumor with a very poor *** this study,we systematically analyzed the DNA methylation alterations of autophagy-related lncRNAs and their association with drug therapies in *** identified 9 DNA methylation-dysregulated lncRNA regulators of autophagy-related genes as autophagy-related lncRNAs.A dysregulated regulatory network consisting of 9 autophagy-related lncRNAs and 237 differentially expressed autophagy-related genes was *** of small molecule drug candidates that may affect DNA methylation dysregulated lncRNA activity,including 45 drug lncRNA pairs,involving 7 DNA methylation dysregulated lncRNAs and 43 ***,we identified a DNA methylation-dysregulated autophagy-related lncRNA MIR155HG as an independent prognostic indicator for GBM.

关键词： regulated alterations drugs

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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Chinese Medical Journal 2024年第7期137卷 859-870页

作者： Xianlong Wang Chuan Zhao Jincheng Lin Hongxing Liu Qiuhong Zeng Huadong Chen Ye Wang Dapeng Xu Wen Chen Moping Xu En Zhang Da Lin Zhixiong Lin Department of bioinformatics School of Medical Technology and EngineeringKey Laboratory of Medical BioinformaticsKey Laboratory of Ministry of Education for Gastrointestinal CancerFujian Medical UniversityFuzhouFujian 350122China Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China

Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar *** effective drug is available and interpatient heterogeneity is *** study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles,imaging findings,and histological features,in order to predict the response to anti-inflammatory treatment and ***:Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled,including 119 ACPs and 23 papillary ***-exome sequencing(151 tumors,including recurrent ones),RNA sequencing(84 tumors),and DNA methylome profiling(95 tumors)were *** clustering and non-negative matrix factorization were used for subgrouping,and Cox regression were utilized for prognostic evaluation,***:Three distinct molecular subgroups were identified:WNT,ImA,and *** WNT subgroup showed higher Wnt/β-catenin pathway activity,with a greater number of epithelial cells and more predominantly solid *** ImA and ImB subgroups had activated inflammatory and interferon response pathways,with enhanced immune cell infiltration and more predominantly cystic ***-activated protein kinases(MEK/MAPK)signaling was activated only in ImA samples,while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group,mostly consisting of *** degree of astrogliosis was significantly elevated in the ImA group,with severe finger-like protrusions at the invasive front of the *** molecular subgrouping was an independent prognostic factor,with the WNT group having longer event-free survival than ImB(Cox,P=0.04).ImA/ImB cases were more likely to respond to immune checkpoint blockade(ICB)therapy than the WNT group(P<0.01).In the preliminary screening of subtyping markers,CD38 was significantly downregulated in WNT compared with ImA and ImB(P=0.01).Conclusions:ACP comprises three molecular subtypes with distinct

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

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World Journal of Diabetes 2024年第5期15卷 814-817页

作者： Ashraf Al Madhoun Department of Genetics and bioinformatics Dasman Diabetes InstituteDasman 15400Kuwait

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose *** persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental *** genomic studies have identified numerous genetic variations associated with an increased risk of ***,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated *** clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy *** findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC *** findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

关键词： Glucokinase regulatory protein rs780094 Type 2 diabetes mellitus Dyslipidemia Non-alcoholic fatty liver disease Nephropathy

Nonlinear system dynamics of calcium and nitric oxide due to cell memory and superdiffusion in neurons

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Communications in Theoretical Physics 2024年第5期76卷 16-32页

作者： Anand Pawar Kamal Raj Pardasani Department of Mathematics Bioinformatics and Computer ApplicationsMaulana Azad National Institute of TechnologyBhopal-462003Madhya PradeshIndia

The integer-order interdependent calcium([Ca^(2+)])and nitric oxide(NO)systems are unable to shed light on the influences of the superdiffusion and memory in triggering Brownian motion(BM)in ***,a mathematical model is constructed for the fractional-order nonlinear spatiotemporal systems of[Ca^(2+)]and NO incorporating reaction-diffusion equations in *** two-way feedback process between[Ca^(2+)]and NO systems through calcium feedback on NO production and NO feedback on calcium through cyclic guanosine monophosphate(cGMP)with plasmalemmal[Ca^(2+)]-ATPase(PMCA)was incorporated in the *** Crank–Nicholson scheme(CNS)with Grunwald approximation along spatial derivatives and L1 scheme along temporal derivatives with Gauss–Seidel(GS)iterations were *** numerical outcomes were analyzed to get insights into superdiffusion,buffer,and memory exhibiting BM of[Ca^(2+)]and NO *** conditions,events and mechanisms leading to dysfunctions in calcium and NO systems and causing different diseases like Parkinson’s were explored in neurons.

关键词： [Ca^(2+)]and nitric oxide signaling reaction-diffusion equations fractional-order systems Grunwald approximation Gauss-Seidel iterations

NeoHunter:Flexible software for systematically detecting neoantigens from sequencing data

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Quantitative Biology 2024年第1期12卷 70-84页

作者： Tianxing Ma Zetong Zhao Haochen Li Lei Wei Xuegong Zhang MOE Key Lab of bioinformatics Bioinformatics Division of BNRIST and Department of AutomationTsinghua UniversityBeijingChina School of Medicine Tsinghua UniversityBeijingChina School of Life Sciences Tsinghua UniversityBeijingChina

Complicated molecular alterations in tumors generate various mutant *** of these mutant peptides can be presented to the cell surface and then elicit immune responses,and such mutant peptides are called *** detection of neoantigens could help to design personalized cancer *** some computational frameworks for neoantigen detection have been proposed,most of them can only detect SNV-and indel-derived *** addition,current frameworks adopt oversimplified neoantigen prioritization *** factors hinder the comprehensive and effective detection of *** developed NeoHunter,flexible software to systematically detect and prioritize neoantigens from sequencing data in different *** can detect not only SNV-and indel-derived neoantigens but also gene fusion-and aberrant splicing-derived *** supports both direct and indirect immunogenicity evaluation strategies to prioritize candidate *** strategies utilize binding characteristics,existing biological big data,and T-cell receptor specificity to ensure accurate detection and *** applied NeoHunter to the TESLA dataset,cohorts of melanoma and non-small cell lung cancer *** achieved high performance across the TESLA cancer patients and detected 79%(27 out of 34)of validated neoantigens in ***-and indel-derived neoantigens accounted for 90%of the top 100 candidate neoantigens while neoantigens from aberrant splicing accounted for 9%.Gene fusion-derived neoantigens were detected in one *** is a powerful tool to‘catch all’neoantigens and is available for free academic use on Github(XuegongLab/NeoHunter).

关键词： cancer vaccine molecular alteration neoantigen neoantigen prioritization

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

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World Journal of Diabetes 2024年第6期15卷 1381-1383页

作者： Chaeyoung Lee Department of bioinformatics and Life Science Soongsil UniversitySeoul 06978South Korea

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with *** particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

关键词： Age-specific difference Cardiovascular disease Genetic heterogeneity by age Genetic susceptibility Prediabetes

Gedunin attenuates streptozotocin-induced diabetic hepatopathy in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 288-297页

作者： Suchismita Mazumdar Thankamani M Marar Jyoti M Patki School of Biotechnology and bioinformatics D.Y.Patil Deemed to be UniversityNavi Mumbai 400614India

Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic ***:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+*** parameters for liver function and liver histology were *** molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock ***:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant *** studies showed considerable restoration of liver architecture in gedunin-treated diabetic *** silico studies revealed stable binding of gedunin with GLUT2 and ***:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative *** studies are warranted to verify the mechanism of its hepatoprotective action.

关键词： Gedunin GLUT2 SGLT1 Diabetic hepatopathy Docking Histology Homology modelling

A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

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Journal of Genetics and Genomics 2024年第8期51卷 836-843页

作者： Shibo Hou Jingheng Chen Ruobing Feng Xuejiao Xu Nan Liang Jackson Champer Center for bioinformatics Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant *** operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a ***,resistance alleles formed by end-joining repair pose a significant *** address this,we create a homing drive targeting the essential hairy gene in Drosophila *** resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of *** drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the ***,the drive does not reach 100%due to the formation of functional resistance alleles despite using four *** alleles have a large deletion but likely utilize an alternate start ***,revised designs targeting more essential regions of a gene may be necessary to avoid such functional *** of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.

关键词： Genedrive Homing drive Rescueelement Population modification Multiplexed gRNAs Resistance alleles Cage study