Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE191298 | GEO | 2021/12/25
REPOSITORIES: GEO
Similar Datasets
Project description:Introduction of new methods requires meticulous evaluation before they can be applied to forensic genetic case work. Here, a custom QIAseq Targeted DNA panel with 164 ancestry informative markers was assessed using the MiSeq sequencing platform. Concordance, sensitivity, and the capability for analysis of mixtures were tested. The assay gave reproducible and nearly concordant results with an input of 10 and 2 ng DNA. Lower DNA input led to an increase in both locus and allele drop-outs, and a higher variation in heterozygote balance. Locus or allele drop-outs in the samples with less than 2 ng DNA input were not necessarily associated with the overall performance of a locus. Thus, the QIAseq assay will be difficult to implement in a forensic genetic setting where the sample material is often scarce and of poor quality. With equal or near equal mixture ratios, the mixture DNA profiles were easily identified by an increased number of imbalanced heterozygotes. For more skewed mixture ratios, the mixture DNA profiles were identified by an increased noise level. Lastly, individuals from Great Britain and the Middle East were investigated. The Middle Eastern individuals showed a greater affinity with South European populations compared to North European populations.
| S-EPMC8548529 | biostudies-literature
Project description:Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma
| PRJNA790925 | ENA
Project description:BACKGORUND & AIMS: Hepatocellular carcinoma (HCC) disproportionally affects Asian Americans due to the high prevalence of chronic hepatitis B virus (HBV) infection and among Asian ethnic groups. The Hmong are diagnosed with HCC at a younger age, with more advanced stage disease, and have the highest cause specific mortality of any Asian ethnic group. Poor survival from HCC has also been associated with differential gene expression in HCC tumors leading us to hypothesize that quantitative traits loci lead to differences in the expression of genes in Hmong which reduce their HCC survival. METHODS: We performed bulk RNA-sequencing of whole blood total RNA from HBV-infected Hmong (n=30) and non-Hmong Asians (Chinese (n=46), and Vietnamese (n=19)). RESULTS: No significant differences between groups were identified in demographic, clinical, or viral factors. A total of 1,491 differentially-expressed transcripts (DETs) were identified across the 3 ethnic groups. When restricted to those with an HBV viral load >2,000 IU/L, 768 DETs were identified and accurately separated individuals by ethincity. Among 273 DETs identified by functional enrichment and pathway analysis and associated with annotated sets of HCC-related genes, 9 were found in 2 gene sets highly expressed in HCC with poor survival. After adjusting for age and sex, expression levels of 4 of these, including CD164, ECT2, HDAC2, and UBE2T, remained significantly elevated in Hmong compared to Chinese and Vietnamese. CONCLUSIONS: These results suggest expression quantitative trait loci predispose Hmong to a more agrressive form of HCC and may explain the poor survival among this Asian ethnic group.
2021-11-01 | GSE173897 | GEO
Project description:Infertility is a global healthcare problem, which affects men and women equally. With the advance of genome-wide analysis, an increasing list of human genes involved in infertility is now available. In order to evaluate the diagnostic interest to analyze these genes, we have designed a gene panel allowing the analysis of 51 genes involved in non-syndromic human infertility. In this initial evaluation study, a cohort of 94 non-syndromic infertility cases with a well-defined infertility phenotype was examined. Five patients with previously known mutations were used as positive controls. With a mean coverage of 457×, and 99.8% of target bases successfully sequenced with a depth coverage over 30×, we prove the robustness and the quality of our panel. In total, we identified pathogenic or likely pathogenic variations in eight patients (five male and three female). With a diagnostic yield of 8.5% and the identification of a variety of variants including substitution, insertion, deletion, and copy number variations, our results demonstrate the usefulness of such a strategy, as well as the efficiency and the quality of this diagnostic gene panel.
| S-EPMC7999157 | biostudies-literature
Project description:Parentage testing is routinely performed by genotyping short tandem repeat (STR) through capillary electrophoresis in the present. However, ambiguous or even misjudged paternity based on STRs happens from time to time in cases where only one putative parent is available. We analyzed STR data of 7,818,969 unrelated pairs and 75 close-relative pairs and found that although the probability of a random false match between non-relatives was 4.22 × 10-6, the incidence of false or ambiguous paternity results between children and first-degree relatives of their true parent was as high as 18.67%. These results highlight the risk of false inclusion of a relative or even non-relatives in parentage testing with STRs. We then validated all ambiguous STR results by targeted sequencing with a custom panel containing 4,830 individual identification single nucleotide polymorphisms (IISNP), found that the ratio of mismatch loci to total SNPs was 1.78-6.95% in close relatives compared with 10.93-13.49% in unrelated pairs. Last, we reported three real cases with undetermined paternity by STRs and rectified them by dissecting with our IISNP panel. These results suggested that high-density IISNP panel can be used to identify and rectify misjudged cases effectively.
| S-EPMC7937934 | biostudies-literature
Project description:Despite being immune cells of the central nervous system (CNS), microglia contribute to CNS development, maturation, and homeostasis, and microglia dysfunction has been implicated in several neurological disorders. Recent advancements in single-cell studies have uncovered unique microglia-specific gene expression. However, there is a need for a simple yet elegant multiplexed approach to quantifying microglia gene expression. To address this, we have designed a NanoString nCounter technology-based murine microglia-specific custom codeset comprising 178 genes. We analyzed RNA extracted from ex vivo adult mouse microglia, primary mouse microglia, the BV2 microglia cell line, and mouse bone marrow monocytes using our custom panel. Our findings reveal a pattern where homeostatic genes exhibit heightened expression in adult microglia, followed by primary cells, and are absent in BV2 cells, while reactive markers are elevated in primary microglia and BV2 cells. Analysis of publicly available data sets for the genes present in the panel revealed that the panel could reliably reflect the changes in microglia gene expression in response to various factors. These findings highlight that the microglia panel used offers a swift and cost-effective means to assess microglial cells and can be used to study them in varying contexts, ranging from normal homeostasis to disease models.
| S-EPMC11012202 | biostudies-literature
Project description:BackgroundIn the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel.MethodsWe designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC).ResultsEighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis.ConclusionsOur results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.
| S-EPMC7288470 | biostudies-literature
Project description:Diabetic kidney disease (DKD) has been pointed out as a prominent cause of chronic and end-stage renal disease (ESRD). There is a genetic predisposition to DKD, although clinically relevant loci are yet to be identified. We utilized a custom target next-generation sequencing 70-gene panel to screen a discovery cohort of 150 controls, DKD and DKD-ESRD patients. Relevant SNPs for the susceptibility and clinical evolution of DKD were replicated in an independent validation cohort of 824 controls and patients. A network analysis aiming to assess the impact of variability along specific pathways was also conducted. Forty-eight SNPs displayed significantly different frequencies in the study groups. Of these, 28 with p-values lower than 0.01 were selected for replication. MYH9 rs710181 was inversely associated with the risk of DKD (OR = 0.52 (0.28-0.97), p = 0.033), whilst SOWAHB rs13140552 and CNDP1 rs4891564 were not carried by cases or controls, respectively (p = 0.044 and 0.023). In addition, the RGMA rs1969589 CC genotype was significantly correlated with lower albumin-to-creatinine ratios in the DKD patients (711.8 ± 113.0 vs. 1375.9 ± 474.1 mg/g for TC/TT; mean difference = 823.5 (84.46-1563.0); p = 0.030). No biological pathway stood out as more significantly affected by genetic variability. Our findings reveal new variants that could be useful as biomarkers of DKD onset and/or evolution.
| S-EPMC8702126 | biostudies-literature
Project description:Targeted RNASeq using a custom panel of metabolic genes
| PRJNA605015 | ENA
Project description:Purpose: The purpose of this experiment was to determine the time point following activation at which greatest transcriptional differences in metabolic genes were observed between primary human CD4+ T cells treated with metformin + 2-deoxyglucose combination regimen and cells treated with vehicle. Methods: Targeted RNA-Seq data was generated from primary human CD4+ T cell mRNA using a Qiagen custom designed panel of metabolic genes and the Illumina TruSeq stranded mRNA prep. Results: We obtained differential gene expression between metformin + 2-deoxyglucose and vehicle-treated cells using the DESeq2 app in Illumina Basespace for a set of metabolic genes during different time points following activation, and found the greatest changes at 24hr.
2020-06-15 | GSE144352 | GEO