Search results for "Sequencing"
showing 10 items of 1087 documents
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
2012
Background: Accurate outcome prediction in neuroblastoma, which is necessary to enable the optimal choice of risk-related therapy, remains a challenge. To improve neuroblastoma patient stratification, this study aimed to identify prognostic tumor DNA methylation biomarkers.Results: To identify genes silenced by promoter methylation, we first applied two independent genome-wide methylation screening methodologies to eight neuroblastoma cell lines. Specifically, we used re-expression profiling upon 5-aza-2'-deoxycytidine (DAC) treatment and massively parallel sequencing after capturing with a methyl-CpG-binding domain (MBD-seq). Putative methylation markers were selected from DAC-upregulated …
A familial disorder of altered DNA-methylation
2014
BackgroundIn a subset of imprinting disorders caused by epimutations, multiple imprinted loci are affected. Familial occurrence of multilocus imprinting disorders is rare.Purpose/objectiveWe have investigated the clinical and molecular features of a familial DNA-methylation disorder.MethodsTissues of affected individuals and blood samples of family members were investigated by conventional and molecular karyotyping. Sanger sequencing and RT-PCR of imprinting-associated genes (NLRP2, NLRP7, ZFP57, KHDC3L, DNMT1o), exome sequencing and locus-specific, array-based and genome-wide technologies to determine DNA-methylation were performed.ResultsIn three offspring of a healthy couple, we observed…
Applications of alignment-free methods in epigenomics
2013
Epigenetic mechanisms play an important role in the regulation of cell type-specific gene activities, yet how epigenetic patterns are established and maintained remains poorly understood. Recent studies have supported a role of DNA sequences in recruitment of epigenetic regulators. Alignment-free methods have been applied to identify distinct sequence features that are associated with epigenetic patterns and to predict epigenomic profiles. Here, we review recent advances in such applications, including the methods to map DNA sequence to feature space, sequence comparison and prediction models. Computational studies using these methods have provided important insights into the epigenetic reg…
Mutant Plasticity Related Gene 1 (PRG1) acts as a potential modifier in SCN1A related epilepsy
2018
ABSTRACTPlasticity related gene 1 encodes a cerebral neuron-specific synaptic transmembrane protein that modulates hippocampal excitatory transmission on glutamatergic neurons. In mice, homozygous Prg1-deficiency results in juvenile epilepsy. Screening a cohort of 18 patients with infantile spasms (West syndrome), we identified one patient with a heterozygous mutation in the highly conserved third extracellular phosphatase domain (p.T299S). The functional relevance of this mutation was verified by in-utero electroporation of a mutant Prg1 construct into neurons of Prg1-knockout embryos, and the subsequent inability of hippocampal neurons to rescue the knockout phenotype on the single cell l…
The SARS-CoV-2 envelope (E) protein has evolved towards membrane topology robustness.
2021
- Single-spanning SARS-CoV-2 envelope (E) protein topology is a major determinant of protein quaternary structure and function. - Charged residues distribution in E protein sequences from highly pathogenic human coronaviruses (i.e., SARS-CoV, MERS-CoV and SARS-CoV-2) stabilize Ntout-Ctin membrane topology. - E protein sequence could have evolved to ensure a more robust membrane topology from MERS-CoV to SARS-CoV and SARS-CoV-2.
On the power and the systematic biases of the detection of chromosomal inversions by paired-end genome sequencing
2013
One of the most used techniques to study structural variation at a genome level is paired-end mapping (PEM). PEM has the advantage of being able to detect balanced events, such as inversions and translocations. However, inversions are still quite difficult to predict reliably, especially from high-throughput sequencing data. We simulated realistic PEM experiments with different combinations of read and library fragment lengths, including sequencing errors and meaningful base-qualities, to quantify and track down the origin of false positives and negatives along sequencing, mapping, and downstream analysis. We show that PEM is very appropriate to detect a wide range of inversions, even with …
Exome sequencing of three cases of familial exceptional longevity
2014
Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Inter…
Molecular and patho-physiological basis of syndromes with developmental anomalies and intellectual disability
2013
Intellectual disability (ID) corresponds to abnormal intellectual performances and adaptive functions, beginning in childhood. It is estimated that 2-3% of individuals develop a ID, which represents a significant medical challenge since people with ID are frequently in situations of social dependence. Overall, a critical involvement of genetic factors in this disease is suspected. To date, several hundreds of genes are known to be responsible for ID. The ID is particularly characterized by extreme clinical and genetic heterogeneity, that made it resistant to conventional genetic studies. However, it is classicaly separated between syndromic ID, which may be clinically recognizable due to as…
Next-Generation Sequencing (NGS)-Based Measurable Residual Disease (MRD) Monitoring in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication (…
2020
Background: FLT3-ITD occurs in ~25% of adult AML patients (pts) and is associated with poor prognosis. MRD monitoring is of high prognostic relevance, but restricted to certain AML subtypes. FLT3-ITD represents an attractive target for MRD monitoring in particular in pts treated with a tyrosine kinase inhibitor. FLT3-ITD MRD monitoring is hampered by the broad heterogeneity of ITD length and insertion site (IS). NGS may overcome these limitations offering the opportunity for MRD monitoring in FLT3-ITD+ AML. Aims: To validate our recently established NGS-based FLT3-ITD MRD assay in a defined cohort of FLT3-ITD+ AML pts treated within the AMLSG16-10 trial (NCT01477606) combining intensive che…
AnySeq: A High Performance Sequence Alignment Library based on Partial Evaluation
2020
Sequence alignments are fundamental to bioinformatics which has resulted in a variety of optimized implementations. Unfortunately, the vast majority of them are hand-tuned and specific to certain architectures and execution models. This not only makes them challenging to understand and extend, but also difficult to port to other platforms. We present AnySeq - a novel library for computing different types of pairwise alignments of DNA sequences. Our approach combines high performance with an intuitively understandable implementation, which is achieved through the concept of partial evaluation. Using the AnyDSL compiler framework, AnySeq enables the compilation of algorithmic variants that ar…