Unlabelled: We introduce a new divide and conquer approach to deal with the problem of de novo genome assembly in the presence of ultra-deep sequencing data (i.e. coverage of 1000x or higher). Our proposed meta-assembler Slicembler partitions the input data into optimal-sized 'slices' and uses a standard assembly tool (e.g. Velvet, SPAdes, IDBA_UD and Ray) to assemble each slice individually. Slicembler uses majority voting among the individual assemblies to identify long contigs that can be merged to the consensus assembly. To improve its efficiency, Slicembler uses a generalized suffix tree to identify these frequent contigs (or fraction thereof). Extensive experimental results on real ultra-deep sequencing data (8000x coverage) and simulated data show that Slicembler significantly improves the quality of the assembly compared with the performance of the base assembler. In fact, most of the times, Slicembler generates error-free assemblies. We also show that Slicembler is much more resistant against high sequencing error rate than the base assembler.
Availability And Implementation: Slicembler can be accessed at http://slicembler.cs.ucr.edu/.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765875 | PMC |
http://dx.doi.org/10.1093/bioinformatics/btv226 | DOI Listing |
Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent DNA methylation changes are regional and occur at multiple adjacent CpG sites, either stochastically or in a coordinated block-like manner. Deep learning analysis of single-molecule patterns in two genomic loci achieved accurate age prediction with a median error of 1.
View Article and Find Full Text PDFJAC Antimicrob Resist
December 2024
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
Introduction: We assessed the kinetics of the clearance of integrase strand transfer inhibitors resistance mutations (INSTIs-RMs) and associated factors from people living with HIV (PWH) displaying suppressed viral replication after virological failure (VF) on an INSTI regimen.
Patients And Methods: We included PWH with HIV-RNA viral loads ≤20 copies/mL for at least 5 years in whom INSTIs-RM had been identified at least once in a prior RNA resistance genotyping test. HIV DNAs were sequenced by Sanger sequencing (SS) and ultra-deep sequencing (UDS; detection threshold: 5%) every year over the preceding 5 years.
Nat Commun
November 2024
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.
View Article and Find Full Text PDFBiomark Res
November 2024
Sahlgrenska Center for Cancer Research, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma.
View Article and Find Full Text PDFSci Rep
November 2024
Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, 1000, Slovenia.
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