15028 results for "cancer studies using rna-seq"

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• Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium

  The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate at a single-cell level the impact of several media (e.g. BEGMTM, PneumaCultTM, “Half&Half” and “Clancy”) on cell type distribution. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling or epithelial shape. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretomes transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cells fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the phenomenon to be investigated such as cilia or mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and shaping.

  Study EGAS00001007572

• Long-read whole genome sequencing of gastric cancer

  Gastric cancer (GC) remains a significant health challenge globally, with a particularly high incidence in Asia, including Singapore. Understanding the genomic landscape of normal gastric and the different GC subtypes along with its precursor lesions such as intestinal metaplasia (IM) as well as GC metastatic sites is crucial for advancing diagnostics, prognostics, and therapeutics. Long-read sequencing technologies offer an opportunity to delve deeper into the genomic and epigenetic alterations underlying these conditions and to complement existing short-read omics data. By integrating these data with previously generated in-house multi-omics data (such as RNA sequencing and whole exome sequencing), we hope to better elucidate the molecular mechanism underlying GC initiation and progression.

  Study EGAS50000001607

• Application of targeted long-read methylation sequencing to dissected lung cancer tissues

  To investigate DNA methylation patterns within the tumor microenvironment, multiple regions were dissected from fresh-frozen sections of two lung adenocarcinoma specimens using the Millisect system. These regions were annotated based on spatial transcriptome data. DNA samples extracted from these regions were subjected to targeted long-read methylation sequencing using t-nanoEM. To establish a control dataset, short-read whole-genome sequencing (WGS) was performed on the tumor and normal parts, and long-read WGS was performed on the tumor part.

  Study JGAS000757

• Center for Craniofacial and Dental Genetics: Study of Dental Caries and Cleft Lip/Palate in Guatemala

  This study provides an opportunity to investigate the genetics of both dental caries and orofacial clefts (OFCs) in one set of families ascertained in Guatemala. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). Furthermore this study brings together multiple research priorities of the University of Pittsburgh Center for Craniofacial and Dental Genetics (www.ccdg.pitt.edu). A genome-wide panel of 610,000 SNPs was genotyped at the Broad Institute to be comparable to our other pertinent GENEVA studies that are also part of dbGaP (dbGaP accession number phs000095, "Dental Caries: Whole Genome Association and Gene x Environment Studies" and dbGaP accession number phs000094, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). The goal of this study is to investigate genetic determinants to dental caries and to OFCs in a novel study population. To date, most genetic studies of dental caries have been conducted in Caucasians, and of OFCs in Caucasians and Asians. The Guatemalan population under study is rural and ethnically mixed with a high proportion of Native-South-Americans. Thirty-six Guatemalans from this dataset were also part of the recent GWAS studies of cleft lip and cleft palate (Beaty et al., 2010 and 2011, dbGaP Study Accession: phs000094, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). In addition to the families ascertained in Guatemala, some subjects were genotyped with this cohort to augment the data in the parent GENEVA study (Dental Caries: Whole Genome Association and Gene x Environment Studies, dbGaP accession number phs000095), in particular individuals from the IOWA and PITT GENEVA study sites. Their data are available with the parent study. Dental caries (also known as tooth decay) remains the most common chronic disease of childhood, five times more common than asthma and seven times more common than environmental allergies, with more than 40% of children exhibiting caries when they enter kindergarten. In 2005, it was estimated that dental health care costs were approximately $84 billion, of which 60% or about $50 billion were related to treatment of dental caries. The etiology of dental caries has been studied for many years. Multiple factors contribute to a person's risk for caries, including: 1) environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and 2) host factors such as salivary flow, salivary buffering capacity, position of teeth relative to each other, surface characteristics of tooth enamel and depth of occlusal fissures on posterior teeth. In spite of all that is known about this disease, there are still individuals who appear to be more susceptible to caries and those who are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Other recent studies of twins reared together estimated the heritability for caries, adjusted for age and gender, as ranging from 45-64%. In our study populations of families, we also estimated caries heritability as approximately 54%-70% of variation in primary dentition caries scores and 35%-55% in the permanent dentition (Wang et al., 2010). Orofacial clefts (OFCs), particularly cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP) are a major public health problem, affecting one in every 500-1000 births worldwide thus representing the most common facial birth defect and one of the most common of all congenital anomalies. CL/P is a major structural birth defect that is notable for significant lifelong morbidity and complex etiology. The extensive psychological, surgical, speech and dental involvement emphasize the importance of understanding the underlying causes of CL/P. Therefore, many research groups have attempted to elucidate the etiology of CL/P, with some recent success by our research group and others (see Beaty et al., 2010, 2011; Dixon et al., 2011). It is clear that CL/P can occur as part of Mendelian syndromes, that certain chromosomal abnormalities include CL/P in the phenotype, and that certain teratogens can increase the risk of having an offspring with CL/P. However, phenotypes of known etiology comprise only a small portion of all individuals with a CL/P or CP, and the major focus of research into OFCs is to develop an understanding of the etiology of nonsyndromic (NS) forms of clefting. A major focus of the University of Pittsburgh CCDG has been to study additional phenotypes within nonsyndromic OFC families in order to identify sub-clinical expressions of OFC risk genes or risk variants, e.g. SNPs (see Weinberg et al., 2006). A detailed oral exam is conducted as part of these extended phenotypic studies, including a dental caries exam. Note that although there are some reports in the literature of higher caries experience in individuals with clefts, the most recent meta-analysis of those literature reports concluded that individuals born with these defects do not have a higher frequency of caries (Hasslöf and Twetman, 2007). Notably, we investigated the association of CL/P and caries in three of our study populations (including part of the Guatemalan population in this GWAS study) and also found no increase in caries rates of CL/P cases versus controls (Jindal et al., 2011). This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to dental caries and oral clefts through large-scale genome-wide association studies of well-characterized Guatemalan families and individuals. Genotyping was performed at the Broad Institute of MIT and Harvard. The study was supported by the National Institute of Dental and Craniofacial Research (NIDCR, U01-DE018903). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000440

• Comparing nodal versus bony metastatic spread using tumour phylogenies

  The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extra-prostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extra-prostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.

  Study EGAS00001001801

• Single cell RNA sequencing of colorectal cancer patients (KUL5)

  All libraries were sequenced on Illumina NextSeq or NovaSeq6000 until sufficient saturation was reached.

  Dataset EGAD00001008585

• Sequencing data for oesophageal and related samples - Mourikis et al (RNA)

  Data supporting: "Patient-specific detection of cancer genes reveals recurrently perturbed processes in esophageal adenocarcinoma." Mourikis et al. RNAseq (BAM files) 137 samples

  Dataset EGAD00001004776

• EPITREAT pilot cohort

  Benchmark data set containing five tumor/normal pairs of non-small cell lung cancer (NSCLC) patients. Tissue pairs were screened with bisulfite (BS) sequencing, MeDIP methylation enrichment sequencing and RNA sequencing in order to identify differentially methylated and expressed spots in the genomes.

  Dataset EGAD00001003116

• Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma

  Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials.

  Study EGAS50000001217

• (h)MeDIP-Seq of high-risk prostate cancer

  Immunoprecipitation of methylated and hydroxymethylated DNA was performed on DNA isolated from tumoral and non-tumoral prostate tissue of patients with high-risk disease. Samples were sequenced on the Illumina HiSeq as 50 bp single end.

  Study EGAS00001001019

• Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics

  Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

  Study EGAS00001006567

• cfMeDIP data for 67 VPC samples

  We analyzed the cell free DNA methylomes using 67 plasma samples from patients with mCRPC prostate cancer in the VPC project. Methylation was profiled using the methylated DNA immunoprecipitation coupled to next generation sequencing (MeDIP) technology.

  Dataset EGAD00001008711

• CancerLocator: Non-Invasive Cancer Diagnosis and Tissue-of-Origin Prediction Using Methylation Profiles of Cell-Free DNA

  Background: The detection and characterization of cell-free DNA in plasma is one of the most promising new areas in cancer diagnosis. Liquid biopsy, unlike traditional tissue biopsy, has the potential to diagnose a variety of different malignancies. Results: Here we propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. We comprehensively evaluate CancerLocator with simulations and real data, and compare its performance with that of two established multi-class classification methods. We show that the predicted tumor burdens are highly consistent with the true values. In addition, when the proportion of tumor-derived DNAs in the cell-free DNAs is low, the two popular machine learning methods completely fail for cancer diagnosis, while CancerLocator successfully overcomes the challenge. CancerLocator also achieves promising results on patient plasma samples, despite the fact that the DNA methylation data from these samples has very low sequencing coverage. Conclusions: CfDNA methylation may be developed as an important approach for non-invasive early cancer diagnosis.

  Study EGAS00001002211

• CancerDetector: Ultrasensitive and Non-Invasive Cancer Detection at the Resolution of Individual Reads using Cell-free DNA Methylation Sequencing Data

  The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed “CancerDetector”, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation patterns of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor burden. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor DNAs. In addition, the predicted tumor burden showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1X to 10X). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.

  Study EGAS00001002728