Developing high throughput single-cell single-nucleotide in situ pairwise sequencing for macromolecule spatail-omics
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE190219 | GEO | 2023/12/01
REPOSITORIES: GEO
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Project description:Primary Objective:
Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.
Secondary Objectives:
Correlation of SNP profile with indicators of tumour response parameters, such as radiological response, duration of response, time to progression (TTP), overall survival (OS) time, incidence of non-dermatological adverse events.
| 2135070 | ecrin-mdr-crc
Project description:Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. SNP genotype analysis of Affymetrix 6.0 Chip. SNP arrays was performed for 22 Chinese patients with Osteonecrosis of the Femoral Head.
2014-07-28 | E-GEOD-58951 | biostudies-arrayexpress
Project description:Primary outcome(s): To investigate the association between the efficacy of oxaliplatin for liver metastasis and SNP of ERCC1-118 in colorectal cancer patients.
| 2617967 | ecrin-mdr-crc
Project description:Isogenic, toxin B (tcdB) mutants of two independently isolated erythromycin-sensitive derivatives (630E and 630Δerm) of the Clostridium difficile strain CD630 have previously been shown to behave differently in the hamster model of infection. Those based on strain 630E failed to cause disease, whereas those based on 630Δerm did. Here we show that whilst 630Δerm and its derivatives behave in a comparable way to the parental strain CD630 in terms of growth rate, motility, sporulation, toxin production and virulence, strain 630E and its derivatives do not. They grow more slowly, achieve lower final cell densities, exhibit a reduced capacity for spore formation, express lower levels of toxin and are less virulent in the hamster model. Using Next Generation Sequencing, a total of three SNPs were found that were in both CD630 and 630Δerm. In addition to these, 630Δerm had eight unique SNPs compared to CD630 and 630E, while 630E had 11 SNPs not found in the other two strains. The strain-specific SNPs most likely arose during the repeated subculture experiments undertaken to isolate these ermB deletion strains. The relatively large number of mutations present meant that the identification of those SNPs responsible for the altered properties of 630E was not possible. Allelic exchange was used to correct three mutational changes in 630E, but with essentially no effect on phenotype. These were a 150 bp inversion in the promoter region of a flagella operon, the truncation of CD630_12740 (topoisomerase I), and the correction of a SNP that results in the fusion of two components of a glucose phosphor-transferase-system. To complete the analysis we performed RNAseq, comparing the transcriptome of the three strains at three different time points. The finding corroborated the many differences between the strains, but also highlighted that one SNP cannot necessarily be attributed to one particular expression pattern or even phenotype. In conclusion 630Δerm more accurately mirrors the behaviour of the parental strain CD630, hence if genetic-based studies with C. difficile strain CD630 are necessary, then the use of strain 630∆erm should be favoured over strain 630E. At a fundamental level, our data underlines the importance of effective strain curation and the need to genome re-sequence master seed banks wherever possible.
2016-09-28 | GSE72006 | GEO
Project description:Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely-related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). We hypothesised that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites (TSS) of the ST313 strain D23580, and searched for a gene expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance and modulated virulence in the chicken infection model. We propose that high levels of expression PgtE of by African S. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection. Our finding of a functional role for an extra-genic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on non-coding regions of the genome.
2017-12-15 | GSE108104 | GEO
Project description:Over 90% of disease associated single nucleotide polymorphisms (SNPs) identified by genome wide association studies (GWAS) are noncoding variants. Platform to efficiently validate the biological function of variants thus discovered remain distinctly lacking. Here, we used β-like cells derived from isogenic human pluripotent stem cells (hPSCs), carrying the type 1 diabetes (T1D)-associated noncoding SNP rs2542151T>G or the knockout of the SNP-associated gene PTPN2−/−, to systematically examine the role of the T1D associated noncoding variant in β cell function and survival. PTPN2−/− and rs2542151T>G both decrease insulin production and elevate cell apoptosis in vitro as well as in vivo. A high content chemical screen identified sodium butyrate, a short-chain fatty acid, to rescue the defects of PTPN2−/−and rs2542151G/G β-like cells in vitro and a humanized mouse model. The combined phosphoproteomics, proteomics and RNA-seq analyses discovered a LAMIN A/HDAC/ERK/complex 1 axis as the downstream pathway of PTPN2 to control β cell survival. Together, this study proved the principle to apply hPSC-derived β cells to study diabetes associated noncoding SNP, and identified a drug candidate for the precision therapy of T1D.
2021-03-22 | GSE166785 | GEO
Project description:Purpose: Water stress limits plant survival and production in many parts of the world. Identification of genes and alleles responding to water stress conditions is important in breeding plants better adapted to drought. Currently there are no studies examining the transcriptome wide gene and allelic expression patterns under water stress conditions. We used RNA sequencing (RNA-seq) to identify the candidate genes and alleles and to explore the evolutionary signatures of selection Methods: We studied the effect of water stress on gene expression in Eucalyptus camaldulensis seedlings derived from three natural populations. We used reference-guided transcriptome mapping to study gene expression. Reads mapping to predicted transcripts were analysed with edgeR pacakge to study differntial expression of genes under control and water-stress conditions. SNPs within the genes were obtained using pileup file generated with samtools and the SNP frequencies were analysed with VarScan package. SNPs were further characterised as sysnonymous and non-synonymous using popoolation2 pacakge. Results: Several genes showed differential expression between control and stress conditions. Gene ontology (GO) enrichment tests revealed up-regulation of 140 stress-related gene categories and down-regulation of 35 metabolic and cell wall organisation gene categories. More than 190,000 single nucleotide polymorphisms (SNPs) were detected and 2737 of these showed differential allelic expression. Allelic expression of 52% of these variants was correlated with total gene expression. Signatures of selection patterns were studied by estimating the proportion of nonsynonymous to synonymous substitution rates (Ka/Ks). The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that most of the genes are under purifying selection. Among the positively selected genes (Ka/Ks > 1.5) apoptosis and cell death categories were enriched. Of the positively selected genes, ninety genes showed differential expression and 27 SNPs from 17 positively selected genes showed differential allelic expression between treatments. Conclusions: Correlation of allelic expression of several SNPs with total gene expression indicates that these variants may be the cis-acting variants or in linkage disequilibrium with such variants. Enrichment of apoptosis and cell death gene categories among the positively selected genes reveals the past selection pressures experienced by the populations used in this study. Leaf mRNA of 12 samples were used to study the gene expression under control and water-stress conditions. Three samples under water-stress conditions and three samples under control conditions were used as biological replicates for differenctial gene expression between the treatments. High-throughput sequence reads from mRNA samples were generated by deep sequencing with Illumina GAIIx.
2012-07-17 | E-GEOD-39369 | biostudies-arrayexpress
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-02-23 | PXD004435 | Pride
Project description:Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (84.7%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.33; 95% confidence interval: 1.36-13.76) of having coagulation abnormalities than did those without the mutation (wild-type) (p = 0.008). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.
2014-07-28 | GSE58951 | GEO
Project description:Motivation:Recent advances in sequencing technologies promise ultra-long reads of ?100 kb in average, full-length mRNA or cDNA reads in high throughput and genomic contigs over 100 Mb in length. Existing alignment programs are unable or inefficient to process such data at scale, which presses for the development of new alignment algorithms. Results:Minimap2 is a general-purpose alignment program to map DNA or long mRNA sequences against a large reference database. It works with accurate short reads of ?100?bp in length, ?1?kb genomic reads at error rate ?15%, full-length noisy Direct RNA or cDNA reads and assembly contigs or closely related full chromosomes of hundreds of megabases in length. Minimap2 does split-read alignment, employs concave gap cost for long insertions and deletions and introduces new heuristics to reduce spurious alignments. It is 3-4 times as fast as mainstream short-read mappers at comparable accuracy, and is ?30 times faster than long-read genomic or cDNA mappers at higher accuracy, surpassing most aligners specialized in one type of alignment. Availability and implementation:https://github.com/lh3/minimap2. Supplementary information:Supplementary data are available at Bioinformatics online.
| S-EPMC6137996 | biostudies-literature