12505 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

in 20.09 milliseconds.

• RNA-seq, WGS and WES of Hepatocellular carcinomas, enriched in fibrolamellar carcinomas

  DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.

  Study EGAS00001003837

• Heterogeneous Genomic Evolution and Immune Microenvironments in Metastatic Lung Cancer

  The mechanism underlying the occurrence of lung cancer metastasis to different tissues/organs remains elusive. We investigated the genomic evolution and immune microenvironments of paired primary-metastatic tumors by employing multi-region whole-exome sequencing in 179 samples of 106 tumors from 51 lung cancer patients and subsequent immunohistochemistry assays in 70 of them. Our data revealed differences in genomic landscapes, molecular determinants, evolutionary dynamics, and lymphocyte infiltration among different metastatic sites. We demonstrated commonly late arising of metastatic seeding of lung cancer with quantitative evidence. Most distant metastases originated from independent origins of earlier lymph node spreads. Immune-heterogeneity and -homogeneity were primarily driven by arm-level and focal copy number events in primary tumors, respectively. These findings implied the combinatorial role of multiple factors in shaping patterns of dissemination and advanced the clinical evaluation and intervention of lung cancer metastasis.

  Study EGAS00001004228

• Genomic Epidemiology of Complex Diseases in Population-based Brazilian Cohorts

  The EPIGEN-Brasil Initiative is so far the largest Latin American initiative in population genomics and genetic epidemiology. Its main goal is to study the association between genetic variants found in the Brazilian population and complex diseases, taking into account one of the most important characteristics of this population: its admixture. Population genetic include genomewide genotyping of 6487 individuals and high-resolution whole genome sequencing from 30 individuals from three population-based Brazilian cohorts: Salvador, Bambuí and Pelotas. More information about the population-based cohorts are available on: For the 1982 Pelotas birth cohort study in Victora and Barros 2006 (PMID 16373375); For the Bambui cohort study of aging in LIma-Costa MF et al. (2011) (PMID 20805109); For the Salvador-Scaala study in Barreto et al. (2006) (PMID 16796729)

  Study EGAS00001001245

• RNA stability controlled by m6A methylation contributes to X-to-autosome dosage compensation in mammals

  In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared to two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanism of X-to-autosome dosage compensation are still under debate. Here, we show that X-chromosomal transcripts are reduced in m6A modifications and more stable compared to their autosomal counterparts. Acute depletion of m6A selectively stabilises autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.

  Study EGAS00001007112

• Whole Exome and Target Sequencing Data in 75 Samples from 5 Hepatocellular Carcinoma Patients.

  Whole Exome and Target Sequencing Data in 75 Samples from 5 Hepatocellular Carcinoma Patients. The sequencing was performed by Illumina HiSeq 4000. Background and aims: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) could reflect nearly the entire mutation spectrum in given tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC).Methods: Thirty-two multi-regional HCC samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS). ITH extent was measured by the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Matched cfDNAs were also analyzed by WES and TDS. Profiling efficiencies of single tumor specimen and cfDNA were compared and the one better depicted mutational landscape was selected to screen therapeutic targets.Results: We found variable extents of ITH in HCCs and observed branched and parallel evolution patterns. ITH level decreased at higher sequencing depth of TDS than that measured by WES (28.1% vs 34.9%, P < 0.01) but it remained unchanged upon additional samples analyzed. TDS of single tumor specimen detected an average of 70% the total mutations in HCC. Although more mutations were detected in cfDNA under TDS than WES, an average of 47.2% total HCC mutations uncovered by cfDNA suggested tissue outperform cfDNA and the latter may serve as alternative in profiling HCC genome. Consequently, TDS of single tumor tissue in 66 patients and cfDNAs in four unresectable HCCs identified 38.6% (26/66 and 1/4) patients bearing therapeutic targets.Conclusions: TDS of single tumor specimen could largely circumvent ITH to uncover mutations indicative of target therapy in HCC.

  Dataset EGAD00001003278

• Genome-wide cell-free DNA biological patterns in patients with cancer

  The structure of cell-free DNA (cfDNA) is altered in the blood of cancer patients. From whole genome sequencing we retrieved the cfDNA fragment-end composition using a new software (FrEIA), as well as the cfDNA size and tumor fraction in three independent cohorts (n=925 cancer from >10 types and 321 control samples). At 95% specificity, we detect 72% of cancer samples using at least one cfDNA measure, including 64% of early-stage cancer (n=220). cfDNA detection correlates with a shorter overall (p=0.018) and recurrence-free (p=0.006) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n=396 cancer, 90 controls) achieve a detection accuracy of 82% and AUROC of 96%. In conclusion, harnessing the biological features of cfDNA can improve at no-extra cost the diagnostic performance of liquid biopsies.

  Study EGAS00001007400

• The Etiological Bases of Giftedness: Epidemiological Study of Cognitive Ability in Children in Saudi Arabia

  Recent studies of genetic foundations of cognitive ability rely on large samples (hundreds of thousands) of individuals from relatively outbred populations of mostly European ancestry. Hypothesizing that the genetic foundation of cognitive ability depends on the broader population-specific genetic context, we performed a genome-wide association study and homozygosity mapping of cognitive ability estimates obtained through latent variable modeling in a sample of 354 children from the consanguineous population of Saudi Arabia. Approximately half of the sample demonstrated significantly elevated homozygosity levels indicative of inbreeding, and among those with elevated homozygosity, it was negatively associated with cognitive ability. Further homozygosity mapping identified a specific run, inclusive of the GRIA4 gene, that survived corrections for multiple testing for association with cognitive ability. The results suggest that in a consanguineous population, a notable proportion of the variance in cognitive ability in the normal range in children might be regulated by population-specific mechanisms such as patterns of elevated autozygosity.

  Study phs001884

• Idiopathic Multicentric Castleman Disease Whole Genome Sequencing Project

  Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder driven by excessive production of inflammatory cytokines. Patients can exhibit a wide range of clinical features from mild flu-like symptoms to multiple organ failure and death. Human herpesvirus-8 (HHV-8) is a well-established cause of MCD in individuals who are immunosuppressed due to human immunodeficiency virus infection or other causes. On the other hand, it is not known what causes MCD in otherwise healthy individuals with no evidence of exposure to HHV-8 (idiopathic MCD or iMCD). Although iMCD is most common in 40-60 years old adults, it affects people of all ages and early-onset (childhood or young adulthood) cases have been reported. Germline mutations may underlie iMCD in such cases. Patients with early-onset iMCD and their family members were enrolled in the study. To identify germline mutations that may underlie iMCD, whole-genome sequencing was performed in patients and their biological parents from whom DNA samples were available.

  Study phs001706

• Epigenomics of Patient Outcomes after Aneurysmal SAH

  This project was focused on understanding the pathophysiology following aneurysmal subarachnoid hemorrhage (aSAH). DNA methylation is a key mechanism for regulation of gene expression and function in the adult brain and appears to play an important role in neuroprotection during ischemic events in the brain. Delayed cerebral ischemia (DCI), occurring during the acute phase following aSAH, is a major contributor to the complications that later develop; however, the pathophysiology of DCI and the development of complications is not known. We hypothesize that characterizing the methylome representing the CNS environment post aSAH will clarify the pathophysiology associated with DCI and patient outcomes. The aims of this project focused on the daily genome-wide methylomic changes that occur in DNA representing the CNS for the first 14 days after aSAH, as well as in peripheral blood in a subset of partcipants, and determining if this methylomic data impacts DCI and the development of complications after aSAH.

  Study phs001990

• Wisconsin Longitudinal Study on Aging

  The Wisconsin Longitudinal Study (WLS) is a long-term study of a random sample of men and women, who graduated from Wisconsin high schools in 1957, and their siblings. The WLS panel started out with a panel of 10,317 members from the class of 1957. Over time a second panel of 8,734 randomly selected siblings of the original graduate panel were recruited for the study. Of these combined panel members, 9,027 survived and contributed saliva for genetic analysis. Survey data were collected from the original respondents or their parents in 1957, 1964, 1975, 1992, 2004, and 2011, and from a selected sibling in 1977, 1994, 2005, and 2011. WLS data provide a detailed record of educational, social, psychological, economic, mental and physical health characteristics of a relatively homogeneous population that is almost entirely of Northern and Western European ancestry. Saliva was first collected in 2007-2008 by mail. Additional samples were collected in the course of home interviews that began in March 2010.

  Study phs001157