15034 results for "cancer studies using rna-seq"

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• WGoxBS and SureSelect data of the POPS placenta samples

  We carried out whole-genome oxidative bisulfite sequencing (WGoxBS) in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. The sex-specific differential methylation pattern observed in this region was validated in additional 8 healthy placentas (including 2 from the WGoxBS) using SureSelect in-solution target capture. For WGoxBS, placental genomic DNA (4 µg) from 4 healthy pregnancies was processed to achieve 10 kb fragments with the g-Tube (Covaris), according to the manufacturer's instructions. To increase the number of uniquely sequenced reads, two independent libraries were generated for each individual. Multiplexed sequencing was carried out on the Illumina MiSeq, HiSeq 2000, and HiSeq 2500 instruments with 2x100, 2x50 and 2x125 cycles using MiSeq Reagent Kit v3, HiSeq SBS Kit v3 and HiSeq SBS Kit v4, respectively. For SureSelect in-solution capture, placental genomic DNA (3.5 µg) from 8 healthy pregnancies (including 2 from the WGoxBS) was fragmented by the Covaris S220 system according to the SureSelect Methyl-Seq target enrichment protocol (Agilent). All 8 libraries were pooled and sequenced on the Illumina HiSeq 2500 instrument with 2 × 125 cycles using HiSeq SBS Kit v4 and a single lane of the Illumina HiSeq 4000 instrument with 2 × 150 cycles using HiSeq 3000/4000 SBS Kit following Illumina's guidelines (Illumina Application Note: Epigenetics February 2016).

  Dataset EGAD00001003136

• Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs

  We profile the adult human CNS from distinct regions, sex and ages, for chromatin accessibility at the single-nuclei level. Tissue was collected from 20 different donors (10 male, 10 female) within the ages of 34 to 74 years old. Additionally we performed Single-cell nanoCUT&Tag H3K27ac and H3K27me3 profiling for 4 of the donors and multiome single cell assay (RNA-seq+ATAC-seq) for 2 of the donors. Each donor donated fresh frozen white matter from the following three tissue regions: primary motor cortex (Brodmann area 4, BA4), arbor vitae cerebelli (CB) and fasciculi cuneatus and gracilis from and cervical spinal cord (CSC). Tissue was processed semi-randomly, ensuring that each batch of experiments had a representation of both sexes and all three tissue regions. Completed libraries were again randomly multiplexed during sequencing to minimize batch effects. We also performed micro-C,2 replicates, of iPS human derived cell cultures of human oligodendrocyte precursor cells (hOPC).

  Dataset EGAD50000000410

• Whole genome bisufite sequencing of smoking and non-smoking mother-child pairsBisufite sequencing, RNA-seq and ChIP-Seq data of whole blood samples from smoking and non-smoking mothers and their children at gestation/birth and follow-up years.

  Whole-blood samples of 16 mother-child pairs with differing maternal smoking behaviour were bisulfite treated and sequenced with deep coverage to identify smoking-associated differentially methylated regions.RNA-sequencing and ChIP-sequencing of 4 chromatin marks complete the data set and allow for integrative analyses, functional region annotation and to study the impact of epigenetic changes on gene expression.Longitudinal data spanning several years provides the means to investigate the stability of observed differences of all data types.

  Study EGAS00001000455

• BLUEPRINT: Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity

  Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes (RNA-Seq) and epigenomes (ChIP-Seq H3K4me1,H3K4me3,H3K27ac) in four primary cell types: monocytes, in vitro differentiated naive, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, B-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.

  Dataset EGAD00001001011

• Profiling the genomic landscape and evolutionary history of polyploid giant cancer cells in undifferentiated pleomorphic sarcomas

  In this study, we characterise PGCCs in ten pleomorphic sarcomas and use topographic single-cell DNA sequencing (scDNA-seq) to investigate their genomic landscape. We selected PGCCs based on their nuclear morphology, including mononucleated or multinucleated bizarre, misshapen nuclei, and analysed them at single-cell resolution. Histopathological analysis showed that PGCCs were often randomly distributed throughout the tumour and did not appear in clusters, suggesting that they arise de novo rather than through clonal expansion. scDNA-seq revealed that PGCCs originate from the dominant tumour population and exhibit extensive copy number heterogeneity, either due to subsequent or ongoing chromosomal instability. Both clonal and subclonal chromothripsis-like events were identified in PGCCs, indicating that chromothripsis is a key driver of heterogeneity in these cells and is linked to multinucleation rather than mononuclear PGCC formation.

  Dataset EGAD50000002084

• Platinum Pedigree Consortium Long-Read Sequencing

  Platinum Pedigree Consortium includes whole genome sequencing of blood-derived DNA using five technologies on a 4-generation family. This is the CEPH-Utah (CEU) family 1463 and includes 4 grandparents from 1st generation, 2 parents from 2nd generation, 5 children from 3rd generation, 9 individuals from the 4th generation representing 2 branches of the 3rd generation, and their 2 additional parents. Family was not selected for disease, rather large size to study genetic transmission and human variation.Data available through dbGaP include raw sequence data: PacBio HiFi reads in unaligned BAM formats, Ultra-Long Oxford Nanopore (ONT) reads in FASTQ formats, Illumina sequencing, strand-seq and Element sequencing data in FASTQ format. Additionally, alignment files for HiFi reads mapped to the GRCh38 and CHM13v2.0 reference genomes, as well as de novo genome assemblies generated for this project are included.

  Study phs003793

• Single Cell DNA Methylation Analysis for Forensic Epigenetics

  As part of the Epigenetic CHaracterization and Observation (ECHO) program, the Genomic Analysis Laboratory at the Salk Institute generated the DNA methylation profiles of certain PBMC cell types to determine the change in methylation levels before, during or after exposure to certain biological or chemical agents. Samples from individuals who either handled anthrax in controlled environments or who tested positive to MRSA, MSSA, HIV, COVID-19 or exposed to Flu virus or organophosphates, or control samples were used in single-nucleus methylation (snmC-seq) assays to quantify DNA methylation levels of cytosine residues of the DNA. Around 5-10% cytosine sites were sampled in the assay. Using computational analyses, regions in the genome differentially methylated in response to the exposure were identified. This information can be used to develop diagnostic tools to predict the type of infection or time since exposure.

  Study phs003204

• Multimodal epigenetic sequencing analysis of cell-free DNA identifies biomarkers for ALS diagnosis and progression

  The role of the circulating epigenome in ALS remains understudied. We aim to develop diagnostic and prognostic blood-based biomarkers for Amyotrophic Lateral Sclerosis (ALS) by profiling methylome signatures in circulating cell-free DNA (cfDNA) in 20 sporadic ALS cases, 10 C9orf72-associated ALS cases, 10 asymptomatic C9orf72 expansion carriers, and 21 healthy controls using targeted enzymatic methyl-sequencing (EM-seq) of ~4 million CpG loci. We detected numerous differentially methylated genes, including several implicated in ALS risk and pathobiology, and integrated multiple epigenetic features with our Multimodal Epigenetic Sequencing Analysis (MESA) algorithm, achieving an ROC AUC of 0.91 and detecting ~70% of ALS cases at ~100% specificity. Methylation at a subset of loci also correlated with clinical progression and cerebrospinal-fluid neurofilament levels, supporting the potential of cfDNA-based biomarkers for ALS diagnosis and monitoring.

  Study EGAS50000001267

• Target sequencing of 27 cancer-predisposing genes in Japanese colorectal cancer patients

  Background: National Comprehensive Cancer Network (NCCN) recently recommended germline genetic testing for all pancreatic cancer patients. However, the genes targeted by genetic testing and the feasibility of selecting patients likely to carry pathogenic variants have not been sufficiently verified. The purpose of this study was to genetically characterize Japanese patients and examine whether the current guideline is applicable in this population. Methods: Using targeted sequencing, we analyzed the coding regions of 27 cancer-predisposing genes in 1,005 pancreatic cancer patients and 23,705 controls in Japan. We compared the pathogenic variant frequency between cases and controls and documented the demographic and clinical characteristics of carrier patients. We then examined if it was possible to use machine learning to predict carrier status based on those characteristics. Findings: We identified 205 pathogenic variants across the 27 genes. Pathogenic variants in BRCA2, ATM, and BRCA1 were significantly associated with pancreatic cancer. Characteristics associated with carrier status were inconsistent with previous investigations. Machine learning classifiers had a low performance in determining the carrier status of pancreatic cancer patients, while the same classifiers, when applied to breast cancer data as a positive control, had a higher performance that was comparable to that of the NCCN guideline. Interpretation: Our findings support the clinical significance of multigene panel testing for pancreatic cancer and indicate that at least 3.4% of Japanese patients may respond to poly (ADP ribose) polymerase inhibitor treatments. The difficulty in predicting carrier status suggests that offering germline genetic testing for all pancreatic cancer patients is reasonable.

  Study JGAS000346

• Target sequencing of 27 cancer-predisposing genes in Japanese pancreatic cancer patients

  Background: National Comprehensive Cancer Network (NCCN) recently recommended germline genetic testing for all pancreatic cancer patients. However, the genes targeted by genetic testing and the feasibility of selecting patients likely to carry pathogenic variants have not been sufficiently verified. The purpose of this study was to genetically characterize Japanese patients and examine whether the current guideline is applicable in this population. Methods: Using targeted sequencing, we analyzed the coding regions of 27 cancer-predisposing genes in 1,005 pancreatic cancer patients and 23,705 controls in Japan. We compared the pathogenic variant frequency between cases and controls and documented the demographic and clinical characteristics of carrier patients. We then examined if it was possible to use machine learning to predict carrier status based on those characteristics. Findings: We identified 205 pathogenic variants across the 27 genes. Pathogenic variants in BRCA2, ATM, and BRCA1 were significantly associated with pancreatic cancer. Characteristics associated with carrier status were inconsistent with previous investigations. Machine learning classifiers had a low performance in determining the carrier status of pancreatic cancer patients, while the same classifiers, when applied to breast cancer data as a positive control, had a higher performance that was comparable to that of the NCCN guideline. Interpretation: Our findings support the clinical significance of multigene panel testing for pancreatic cancer and indicate that at least 3.4% of Japanese patients may respond to poly (ADP ribose) polymerase inhibitor treatments. The difficulty in predicting carrier status suggests that offering germline genetic testing for all pancreatic cancer patients is reasonable.

  Study JGAS000327