Complex patterns of the HIV-1 epidemic in Kuala Lumpur, Malaysia: Evidence for expansion of circulating recombinant form CRF33_01B and detection of multiple other recombinants

AbstractThe HIV protease-reverse transcriptase (PR-RT) (1047 bp), gp120-env (891 bp) and gp41-env (547 bp) regions from the plasma of 115 HIV-1-infected patients in Kuala Lumpur (KL), Malaysia were sequenced. Detailed phylogenetic and bootscanning analyses were performed to determine the mosaic structure of the HIV-1 strains and their recombination breakpoint(s). Among the 50 patient samples in which all three regions could be amplified, the HIV-1 CRF01_AE subtype (46%) was predominant followed by subtypes B (10%) and B′ (6%). A total of 9/50 (18%) patients were infected with a CRF01_AE/B inter-subtype recombinant, displaying a recombinant form (RF)PR-RT, CRF01_AEgp120-env and CRF01_AEgp41-env. This RF was derived from the Thai variants of CRF01_AE and B′ subtype, with two distinct B′ subtype segments in the backbone of CRF01_AE, similar to the newly identified CRF33_01B. In addition, one sample demonstrated a close structural relationship with the new CRF33_01B in the PR-RT region but displayed B′ segment in part of the env region (RFPR-RT, CRF01_AE/B′gp120-env and B′gp41-env) indicating continuing evolution of CRF33_01B. The remaining 18% of samples were identified as unique recombinant forms (URFs)

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel

10.1371/journal.pone.0093409PLoS ONE94-POLN

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Exploring the needs and challenges of parents and their children in childhood epilepsy care: A qualitative study

Because of the nature of epilepsy, and the unpredictability of seizure recurrence, epilepsy requires long-term treatment with medications. As a consequence, epilepsy has a negative pervasive impact in children with epilepsy (CWE), and their parents. Hence, our aim was to explore the needs and challenges of parents and their CWE. In-depth interviews (IDIs) were conducted with 15 families (12 mothers and 3 fathers) and 15 CWE (aged 8–18 years). Data were transcribed verbatim and thematically analyzed using the descriptive phenomenology approach. The experiences of parents and their CWE could be divided into two time frames: “experiences during a child's first seizure” and “experiences whilst growing up with epilepsy”. Parents’ main concerns and worries were regarding their child's physical health, psychological and emotional wellbeing, academic achievement, and future. The children's main concerns were restrictions imposed, their interpersonal relationship with peers, and being independent in the future. Parents reported that they needed epilepsy-related information, continuity of care, and a parental support group, while CWE reported that their main needs were independence and autonomy. The views of parents and their child with epilepsy were similar in physical functioning and academic achievement. However, parents and children had different views on how epilepsy impacted on the child emotionally, as well as behavioral and interpersonal relationship with peers

Refractive and biometric status of children born premature without retinopathy of prematurity

A cross-sectional study was undertaken to determine the refractive and biometric status of premature children without Retinopathy of Prematurity (ROP) and full term children. Fifty eight children between the ages of 3 and 7 years (32 children born premature without ROP and another 26 children born full term and normal) were examined. Refractive error, corneal curvature, axial length, anterior chamber depth and crystalline lens thickness were determined. The results revealed that children between the age of 3 years and 7 years were emmetropic, irrespective of whether they were born premature without ROP or full term. However, children born premature without ROP had significantly steeper corneas (t = 3.14, p = 0.0349), shorter axial lengths (t = 3.18, p = 0.0313) and thicker crystalline lens (t = 3.31, p = 0.0256) compared to children born full term within the same age group. This study suggests that compensation in ocular parameters can occur to maintain emmetropia, mainly by adjustment of axial length and corneal curvature