Genetic ancestry in the Northern Cape TB (NCTB) cohort
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ABSTRACT:
PROVIDER: PRJEB76294 | ENA |
REPOSITORIES: ENA
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Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
2022-02-16 | PXD029323 | Pride
Project description:Background and aims: As genome sequencing technologies rapidly expand in capacity and availability, understanding how genetic background in different populations modifies IBD risk will be an important factor in disease prediction, prevention, and treatment. However, most of the datasets that are used to generate polygenic risk scores (PRS) contain predominantly European ancestry patients. To address this, we tested different models for prediction of IBD cases using PRS built using association data from multiple races and also assessed the penetrance of rare very early onset IBD (VEOIBD) SNPs. Methods: PRS were calculated using association data from European, African American, and Ashkenazi Jewish (AJ) studies, as well as a meta-GWAS run using all three association datasets. PRS were then combined using regression modelling to assess which combination of scores was best able to predict IBD status in European, AJ, Hispanic, and African American BioMe Biobank populations. Additionally, rare variants were assessed in genes associated with very early onset IBD, taking into account genetic penetrance in each BioMe population, deleteriousness, and evolutionary conservation. Results: Combining risk scores based on IBD association results from multiple racial populations resulted in improved IBD prediction for every population in BioMe. We also identified highly penetrant rare variants in previously established VEOIBD genes which were predicted to be deleterious, including SNPs in established risk genes such as NOD2 as well as novel variants, including some in LRBA which appear to be particularly relevant for risk of IBD in African Americans.
2021-04-07 | GSE150516 | GEO
Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2â68·9) and a specificity of 80·6% (79·2â82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6â64·3) and a specificity of 82·8% (76·7â86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12â18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.
2016-03-22 | E-GEOD-79362 | biostudies-arrayexpress
Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.
2016-03-22 | GSE79362 | GEO
Project description:Bangladesh multi-drug resistant tuberculosis cohort
| PRJEB39569 | ENA
Project description:Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.
2022-11-09 | GSE211167 | GEO
Project description:True cobras of the genus Naja are venomous snakes with particular medical importance in Africa and Asia. The Cape cobra Naja nivea is one of the most toxic of the African true cobras, but the composition of its venom has rarely been investigated using proteomics methods.
2024-10-08 | PXD036965 | Pride
Project description:Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. The coordinated transcriptional adaptation of carbohydrate metabolism to dietary environmental pressures suggests a genetic and transcriptional mechanism for the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in Americans with African ancestry. Keywords: Ancestry-dependent gene expression, functional genomics, personalized medicine, multi-factoral disease, nutrition, diabetes
2009-10-31 | GSE12959 | GEO
Project description:Igh/Myc translocations underlie both sporadic Burkitt lymphoma (BL) and the endemic clinical form affecting African children infected with malaria. However, while sporadic translocations decapitate Myc from 5' proximal regulatory elements, most endemic events occur hundreds of kilobases away from Myc. The origin of these rearrangements and how they deregulate oncogenes at such distances remain unclear. Here we recapitulate endemic BL-like translocations in plasmacytomas from uracil N-glycosylase (UNG) deficient mice. We demonstrate that in these animals, rare endemic-like translocations arise from non-targeted DNA breaks at Myc loci. Deep-sequencing analyses revealed that the deregulated 3' Igh enhancer alpha physically interacts with and remodels 0.45Mb of translocated chromatin. The results thus explain the long-range deregulation of oncogenes in human and mouse B cell tumors. ChIP-Seq, 4C, and 1 RNASeq samples used to characterize mouse plasmacytoma cell lines and in vitro activated mouse B cells. Biological replicates are present for many of the samples.
2013-07-04 | E-GEOD-48514 | biostudies-arrayexpress
Project description:Study of genes that are differentially spliced and differentially expressed between African Americans and whites with lung squamous cell cancer. Despite racial disparities in lung cancer, the molecular landscape of lung cancer in patients of African ancestry remains underexplored. Population-related differences in alternative RNA splicing have not been explored. We identified differentially spliced genes and differentially expressed genes between lung squamous cell carcinoma from patients of West African and European ancestry.
2021-01-31 | GSE137291 | GEO