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MedRxiv : the Preprint Server For... Oct 2023A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that...
Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes.
A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease, and highlight contemporary challenges and opportunities associated with such efforts.
PubMed: 37873294
DOI: 10.1101/2023.09.30.23296386 -
BMC Medicine Mar 2016Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions... (Review)
Review
BACKGROUND
Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods.
METHODS
We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses.
RESULTS
Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data.
CONCLUSIONS
As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission.
Topics: Bacterial Typing Techniques; Genetic Variation; Genome, Bacterial; Genome-Wide Association Study; Humans; Mycobacterium tuberculosis; Recurrence; Sequence Analysis, DNA; Tuberculosis
PubMed: 27005433
DOI: 10.1186/s12916-016-0566-x -
Medicine May 2020The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and...
BACKGROUND
The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and explore the key pathways and genes of TNBC.
METHODS
The gene expression profiling (GSE86945, GSE86946 and GSE102088) data were obtained from Gene Expression Omnibus Datasets, DEGs were identified by using R software, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools, and the protein-protein interaction (PPI) network of the DEGs was constructed by the STRING database and visualized by Cytoscape software. Finally, the survival value of hub DEGs in breast cancer patients were performed by the Kaplan-Meier plotter online tool.
RESULTS
A total of 2998 DEGs were identified between TNBC and health breast tissue, including 411 up-regulated DEGs and 2587 down-regulated DEGs. GO analysis results showed that down-regulated DEGs were enriched in gene expression (BP), extracellular exosome (CC), and nucleic acid binding, and up-regulated were enriched in chromatin assembly (BP), nucleosome (CC), and DNA binding (MF). KEGG pathway results showed that DEGs were mainly enriched in Pathways in cancer and Systemic lupus erythematosus and so on. Top 10 hub genes were picked out from PPI network by connective degree, and 7 of top 10 hub genes were significantly related with adverse overall survival in breast cancer patients (P < .05). Further analysis found that only EGFR had a significant association with the prognosis of triple-negative breast cancer (P < .05).
CONCLUSIONS
Our study showed that DEGs were enriched in pathways in cancer, top 10 DEGs belong to up-regulated DEGs, and 7 gene connected with poor prognosis in breast cancer, including HSP90AA1, SRC, HSPA8, ESR1, ACTB, PPP2CA, and RPL4. These can provide some guidance for our research on the diagnosis and prognosis of TNBC, and further research is needed to evaluate their value in the targeted therapy of TNBC.
Topics: Data Mining; Databases, Genetic; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Survival Analysis; Triple Negative Breast Neoplasms; Up-Regulation
PubMed: 32358373
DOI: 10.1097/MD.0000000000019986 -
Mutation Research. Reviews in Mutation... 2022Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among... (Review)
Review
Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, in vivo exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.
Topics: Carcinogens; Carcinogens, Environmental; Chromatin; DNA Damage; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 35690411
DOI: 10.1016/j.mrrev.2021.108408 -
Lupus Mar 2022Serological markers such as anti-double stranded (ds)DNA antibodies and complement fractions C3/C4, are integral components of disease activity assessment in patients...
INTRODUCTION
Serological markers such as anti-double stranded (ds)DNA antibodies and complement fractions C3/C4, are integral components of disease activity assessment in patients with systemic lupus erythematosus (SLE). However, it remains uncertain whether treatment should aim at restoration of serological abnormalities.
OBJECTIVES
To analyze and critically appraise the literature on the prognostic impact of active lupus serology despite clinical disease quiescence.
METHODS
A systematic literature review was performed in PubMed and EMBASE using the PICOT(S) (population, index, comparator, outcome(s), timing, setting) system to identify studies evaluating the association of serum anti-dsDNA, C3 and C4 levels assessed at the time of clinical remission or during the disease course, against the risk for impending flares and organ damage. Risk of bias was determined by the Quality in Prognosis Studies and ROB2 tools for observational and randomized controlled studies, respectively.
RESULTS
Fifty-three studies were eligible, the majority having moderate (70.6%) or high (11.8%) risk of bias and not adequately controlling for possible confounders. C3 hypocomplementemia during stable/inactive disease was associated with increased risk (2.0 to 3.8-fold) for subsequent flare in three out of seven relevant studies. Three out of four studies reported a significant effect of C4 hypocomplementemia on flare risk, including one study in lupus nephritis (likelihood ratio-positive 12.0). An increased incidence of flares (2.0 to 2.8-fold) was reported in 11 out of 16 studies assessing the prognostic effect of high anti-dsDNA, and similarly, the majority of studies yielded significant relationships with renal flares. Six studies examined the effect of combined (rather than individual) serological activity, confirming the increased risk (2.0 to 2.7-fold) for relapses. No consistent association was found with organ damage.
CONCLUSION
Notwithstanding the heterogeneity and risk of bias, existing evidence indicates a modest association between abnormal serology and risk for flare in patients with stable/inactive SLE. These findings provide limited support for inclusion of serology in the treat-to-target approach but rationalize to further investigate their prognostic implications especially in lupus nephritis.
Topics: Antibodies, Antinuclear; Complement C4; DNA; Humans; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 35067068
DOI: 10.1177/09612033221074580 -
Neuroscience and Biobehavioral Reviews Jan 2012Schizophrenia (SZ) and bipolar disorder (BPD) have high heritabilities and are clinically and genetically complex. Genome wide association studies (GWAS) and studies of... (Review)
Review
Schizophrenia (SZ) and bipolar disorder (BPD) have high heritabilities and are clinically and genetically complex. Genome wide association studies (GWAS) and studies of copy number variations (CNV) in SZ and BPD have allowed probing of their underlying genetic risks. In this systematic review, we assess extant genetic signals from published GWAS and CNV studies of SZ and BPD up till March 2011. Risk genes associated with SZ at genome wide significance level (p value<7.2 × 10(-8)) include zinc finger binding protein 804A (ZNF804A), major histocompatibility (MHC) region on chromosome 6, neurogranin (NRGN) and transcription factor 4 (TCF4). Risk genes associated with BPD include ankyrin 3, node of Ranvier (ANK3), calcium channel, voltage dependent, L type, alpha 1C subunit (CACNA1C), diacylglycerol kinase eta (DGKH), gene locus on chromosome 16p12, and polybromo-1 (PBRM1) and very recently neurocan gene (NCAN). Possible common genes underlying psychosis include ZNF804A, CACNA1C, NRGN and PBRM1. The CNV studies suggest that whilst CNVs are found in both SZ and BPD, the large deletions and duplications are more likely found in SZ rather than BPD. The validation of any genetic signal is likely confounded by genetic and phenotypic heterogeneities which are influenced by epistatic, epigenetic and gene-environment interactions. There is a pressing need to better integrate the multiple research platforms including systems biology computational models, genomics, cross disorder phenotyping studies, transcriptomics, proteomics, metabolomics, neuroimaging and clinical correlations in order to get us closer to a more enlightened understanding of the genetic and biological basis underlying these potentially crippling conditions.
Topics: Ankyrins; Bipolar Disorder; Calcium Channels, L-Type; DNA Copy Number Variations; Genetic Predisposition to Disease; Humans; Major Histocompatibility Complex; Nerve Tissue Proteins; Schizophrenia; Transcription Factors
PubMed: 21946175
DOI: 10.1016/j.neubiorev.2011.09.001 -
Frontiers in Immunology 2021The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to...
Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.
The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to diversify antigen receptor genes and combat viral infections. These processes, initiated by specific DNA-editing enzymes, often result in mistargeted induction of genome lesions that initiate and drive cancers. Like other molecules involved in human health and disease, the DNA-editing enzymes of the immune system have been intensively studied in humans and mice, with little attention paid (< 1% of published studies) to the same enzymes in evolutionarily distant species. Here, we present a systematic review of the literature on the characterization of one such DNA-editing enzyme, activation-induced cytidine deaminase (AID), from an evolutionary comparative perspective. The central thesis of this review is that although the evolutionary comparative approach represents a minuscule fraction of published works on this and other DNA-editing enzymes, this approach has made significant impacts across the fields of structural biology, immunology, and cancer research. Using AID as an example, we highlight the value of the evolutionary comparative approach in discoveries already made, and in the context of emerging directions in immunology and protein engineering. We introduce the concept of 5-dimensional (5D) description of protein structures, a more nuanced view of a structure that is made possible by evolutionary comparative studies. In this higher dimensional view of a protein's structure, the classical 3-dimensional (3D) structure is integrated in the context of real-time conformations and evolutionary time shifts (4 dimension) and the relevance of these dynamics to its biological function (5 dimension).
Topics: Animals; Biological Evolution; Cytidine Deaminase; DNA; Humans; Protein Conformation; Protein Engineering
PubMed: 34135887
DOI: 10.3389/fimmu.2021.642343 -
Molecular Psychiatry Aug 2020Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by...
Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene-environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case-control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.
Topics: DNA Methylation; Epigenesis, Genetic; Gene-Environment Interaction; Histones; Humans; MicroRNAs; Psychotic Disorders; Schizophrenia
PubMed: 31907379
DOI: 10.1038/s41380-019-0601-3 -
Blood Reviews May 2021Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm with diverse genetic abnormalities and outcomes. To date, DLBCL is invasively diagnosed by tissue...
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm with diverse genetic abnormalities and outcomes. To date, DLBCL is invasively diagnosed by tissue biopsy and few biomarkers are available to predict patient outcome, treatment response and progression. The identification of patient-specific biomarkers would allow a "personalized medicine" approach for DLBCL patients. In this regard, "liquid biopsies" hold great promise, capturing the entire genetic landscape of the tumour and allowing a rapid and dynamic management of cancer. Liquid biopsy studies particularly focus on cell-free nucleic acids, such as cell-free DNA (cfDNA) and microRNAs, which are easy to collect and analyse. In accordance with the PRISMA criteria, we performed a systematic review on circulating nucleic acids as potential biomarkers for DLBCL management. The results suggest that combining information from the genetic (cfDNA) and epigenetic (microRNAs) landscape of the disease could lead to developing an integrated network of non-invasive biomarkers for the better management of DLBCL.
Topics: Biomarkers, Tumor; Circulating MicroRNA; Circulating Tumor DNA; Humans; Liquid Biopsy; Lymphoma, Large B-Cell, Diffuse; RNA, Neoplasm
PubMed: 33229139
DOI: 10.1016/j.blre.2020.100776 -
Genes Jul 2023On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically...
On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically invasive species. Using an analysis that integrates comparative phylogeography, urban landscape genetics, macrogenetics and a systematic review, we explore the worldwide genetic diversity of the human commensal and anthropogenic species and . Based on metadata obtained considering 35 selected studies related to observed heterozygosity, measured by nuclear molecular markers (microsatellites, Single Nucleotide Polymorphisms-SNPs-, restrictition site-associated DNA sequencing -RAD-Seq-), socioeconomic and mobility anthropogenic factors were used as predictors of genetic diversity of and , using the Gini index, principal component analysis and Random Forest Regression as analysis methodology. Population density was on average the best predictor of genetic diversity in the species analyzed, indicating that the species respond in a particular way to the characteristics present in urban environments because of a combination of life history characteristics and human-mediated migration and colonization processes. To create better management and control strategies for these rodents and their associated diseases, it is necessary to fill the existing information gap in urban landscape genetics studies with more metadata repositories, with emphasis on tropical and subtropical regions of the world.
Topics: Humans; Rats; Animals; Population Density; Phylogeography; Introduced Species; Microsatellite Repeats; Polymorphism, Single Nucleotide
PubMed: 37510346
DOI: 10.3390/genes14071442