12377 results for ""statistically+reactive"+taxa+in+microbial+community"

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• Unmapped sequencing reads of EGAD00001007002

  Bam files of unmapped sequencing reads of samples in EGAD00001007002. When utilized in combination with corresponding aligned bam files in dataset EGAD00001007002, they contain all sequencing reads of samples.

  Dataset EGAD00001007647

• Mutation analysis of 10 genes in plasma DNA of RCC patients

  Mutation analysis of 10 frequently mutated genes in renal cell carcinoma (BAP1, KDM5C, MET, MTOR, PBRM1, PIK3CA, PTEN, SETD2, TP53, VHL) in plasma DNA of RCC patients using a custom QIASeq panel (MonRec Cohort)

  Dataset EGAD00001005806

• In Utero MPN Twin WGS Data

  The dataset contains sequencing data generated for the publication 'In utero origin of myelofibrosis presenting in adult monozygotic twins after a prolonged disease latency.

  Dataset EGAD00001008319

• scRNA-seq dataset for AD and Pso patients

  This dataset contains scRNA-seq fastq files to the paper entitled "Single-cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis". The details of experiment setup was described in the paper.

  Dataset EGAD00001010106

• Exome sequencing reads of paediatric glioblastoma

  Whole exome sequencing of paediatric glioblastoma with mutations reported in the manuscript: Mutations in ACVR1, FGFR1 and TP53 associate with tumor location in histone H3 K27M pediatric midline high-grade astrocytoma

  Dataset EGAD00001000792

• Deep-Seq: Resistance to anti-EGFR therapy in colorectal cancer

  In this study we performed ultra deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR in 17 plasma-DNA samples from a total of 10 patients treated with anti-EGFR therapy.

  Dataset EGAD00001000688

• Methylation biomarker study of magnesium deficiency and colorectal cancer

  Five US studies using the Mg tolerance test, the "gold standard" test of Mg status, indicated that >50% participants had Mg deficiency. In our ongoing US trial, we have found a similar result. In growing recognition of the importance of Mg in human health, very recently, Mg was selected by the US Federal Dietary Reference Intake (DRI) Committee to update the DRI. In US and other populations at high risk of Mg deficiency, high Mg intake has been linked to reduced risk of colorectal neoplasia, insulin resistance, metabolic syndrome, type 2 diabetes, and cardiovascular disease (CVD). Conversely, in populations not at high risk of Mg deficiency, high Mg intake has been related to increased risk of total mortality (e.g. total cancer, colorectal cancer, and CVD), particularly when calcium intake is low. These observations suggest that the associations between high Mg intake and disease risks may completely differ by the underlying Mg status. Due to major limitations, the Mg tolerance test is not used in conventional clinical practice and rarely used in research. Instead, serum Mg is used for clinical diagnosis. However, serum Mg performs very poorly at identifying those with Mg deficiency. There is a great need to develop implementable, sensitive, and specific biomarkers which can be easily used for identifying people with Mg deficiency. Without such a marker, it is impossible to develop effective strategies that minimize adverse effects by targeting those who, as a result of Mg deficiency, are at risk of common diseases. It is known that DNA methylation changes are inducible by environmental exposures, including nutrients, and reversible when the exposure disappears. There are two major types of cytosine modifications in DNA, 5-hydroxymethylcytosine (5-hmC) and 5-methylcytosine (5-mC). 5-mC is often associated with suppressed gene expression. 5-hmC, generated by the oxidation of 5-mC, is specifically enriched in expressed genes and plays a critical role in activating and/or maintaining gene expression. However, current epigenomic profiling platforms cannot distinguish 5-hmC from 5-mC. Just recently, our collaborator, Dr. Chuan He (HHMI Investigator), established a novel and state of the art technique, TAB-Seq and TAB-Array protocol, which can separate 5-hmC from 5-mC in the genome. Our pilot studies indicate that Mg intake or treatment significantly affects methylation capacity, 5-mC and 5-hmC biomarkers. Our findings suggest blood leukocyte 5-hmC/5-mC biomarkers may serve as more sensitive biomarkers to identify Mg deficiency than serum Mg. Thus, a comprehensive epigenome-wide association study (EWAS) may help to identify the most sensitive 5-hmC/ 5- mC biomarkers for Mg deficiency. We propose to identify 5-hmC/5-mC biomarkers for Mg deficiency by a 4- phase EWAS study in the "Personalized Prevention of Colorectal Cancer Trial [PPCCT, R01CA149633; PI, Dai and Yu]" with a total of 240 participants. Mg tolerance test will be used as the gold standard. Finally, using newly identified biomarkers, we will evaluate if 12-week Mg treatment reduces TRPM7 expression, essential in Mg homeostasis and colorectal carcinogenesis, in rectal tissues only among those with Mg deficiency.

  Study phs002037

• Investigation of the Causal Etiology in a Patient with T-B+NK+ Immunodeficiency

  We describe a male proband with normal B lymphocyte and natural killer (NK) cell numbers, but who had T lymphopenia beginning at 1 week of age. His peripheral blood contained very few T cell receptor excision circles (TREC), suggesting impaired thymic T cell development. He received an allogeneic hematopoietic stem cell marrow transplant, but despite engraftment, it did not fully correct the T lymphopenia. Sequencing excluded known immunodeficiency genes; however, whole exome sequencing revealed X-linked inheritance by the male proband of a missense mutation in MED14 (MED14V763A), a component of the mediator complex. Functional screening of the MED14V763A variant in zebrafish suggested that MED14 is essential for normal development, since morpholino (MO)-mediated loss of MED14 function attenuated T cell development, but it was rescued by ectopic expression of the wild type human MED14 but not by the MED14V763A variant. This defect in T cell repopulation is consistent with the incomplete T cell reconstitution observed upon transplantation of the proband with bone marrow from his healthy male sibling, who was found to have the same MED14V763A variant. However, the brother was normal, indicating that the altered MED14 could not by itself explain the disease. WES also revealed a mutation in the L1 cell adhesion molecule (L1CAMQ498H); however, introducing that mutation in vivo in mice did not disrupt T cell development. Consequently, the immunodeficiency in the patient is not fully elucidated. It is possible that MED14 contributes, but it is also possible that another gene is fully responsible for the disease.

  Study phs002990

• Liquid Biopsy Versus Tissue Biopsy to Assess Acquired Resistance and Tumor Heterogeneity in Gastrointestinal Cancers

  Tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique molecular resistance alterations in different metastatic lesions in an individual patient, under the selective pressure of therapy1-3. Studies have suggested that liquid biopsy may better capture the heterogeneity of acquired resistance, but systematic, direct comparisons of post-progression liquid vs. standard single-lesion tumor biopsies are lacking. In a prospective cohort of 44 patients with molecularly-defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of post-progression liquid vs. tumor biopsy revealed that liquid biopsy more frequently identified clinically-relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not detected in matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cell-free DNA, tumor biopsies and rapid autopsy specimens elucidated geographic and evolutionary characteristics of heterogeneity. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity and highlight the potential clinical utility of liquid biopsy. Burrell, R. A. & Swanton, C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Molecular oncology 8, 1095-1111, doi:10.1016/j.molonc.2014.06.005 (2014). Misale, S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486, 532-536, doi:10.1038/nature11156 (2012). Ahronian, L. G. et al. Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations. Cancer Disco 5, 358-367, doi:10.1158/2159-8290.Cd-14-1518 (2015).

  Study phs001853

• Tumor Evolution Analysis Uncovered Immune-Escape Related Mutations in Relapsed Diffuse Large B-Cell Lymphoma

  More than 60% of patients with primary diffuse large B-cell lymphoma (DLBCL) achieve durable remissions upon the chemoimmunotherapy with R-CHOP. However, the outcome of the relapse patients is extremely poor. To characterize the molecular features that underlie treatment resistance, we performed whole-exome sequencing (n=44) and deep targeted sequencing (n=27) of 44 diagnosis-relapse DLBCL pairs. We found that the overall landscape of genetic alterations was concordant between diagnosis and relapse DLBCL. By a deep comparison of the longitudinal sequencings, we identified relapse-enriched mutations that involved in evasion of immune surveillance (CD58, TNFRSF14, PKD1, FAS), resistance to DNA damaging agents (ATM, TP53), and critical tumor suppressor gene (ZFHX3). Knockdown of ATM and ZFHX3 resulted in increased drug resistance in both germinal center B cell like (GCB) and activated B cell like (ABC) DLBCL cell lines in vitro, while the knockdown of TNFRSF14 and FAS conferred resistance specifically in GCB cell lines. Furthermore, we summarized two evolutionary patterns of DLBCL relapse as the “durable retention” model with stable clone structure, and the “selective sweep” model which exhibited significant clonal switch. Of note, genetic alterations leading to attenuated immune responses usually presented as trunk mutations in the “durable retention” model (7/12) while were newly acquired or expanded upon relapse in the “selective sweep” model (9/16). Overall, our study demonstrated that relapse DLBCL derives from distinct clonal evolutionary patterns, and highlighted immune escape as an important contributor of tumor relapse.

  Study EGAS50000000032