INDELseek: Detection Of Complex Insertions And Deletions From Next-generation Sequencing Data

BACKGROUND: Complex insertions and deletions (indels) from next-generation sequencing (NGS) data were prone to escape detection by currently available variant callers as shown by large-scale human genomics studies. Somatic and germline complex indels in key disease driver genes could be missed in NGS-based genomics studies. RESULTS: INDELseek is an open-source complex indel caller designed for NGS data of random fragments and PCR amplicons. The key differentiating factor of INDELseek is that each NGS read alignment was examined as a whole instead of 'pileup' of each reference position across multiple alignments. In benchmarking against the reference material NA12878 genome (n = 160 derived from high-confidence variant calls), GATK, SAMtools and INDELseek showed complex indel detection sensitivities of 0%, 0% and 100%, respectively. INDELseek also detected all known germline (BRCA1 and BRCA2) and somatic (CALR and JAK2) complex indels in human clinical samples (n = 8). Further experiments validated all 10 detected KIT complex indels in a discovery cohort of clinical samples. In silico semi-simulation showed sensitivities of 93.7-96.2% based on 8671 unique complex indels in >5000 genes from dbSNP and COSMIC. We also demonstrated the importance of complex indel detection in accurately annotating BRCA1, BRCA2 and TP53 mutations with gained or rescued protein-truncating effects. CONCLUSIONS: INDELseek is an accurate and versatile tool for complex indel detection in NGS data. It complements other variant callers in NGS-based genomics studies targeting a wide spectrum of genetic variations.published_or_final_versio

Consensus on level descriptors for a functional children's eating and drinking activity scale

Aim: To agree wording of level descriptors for a measure of functional outcome of children's eating and drinking. Method: An online, modified Delphi method was used to gather feedback on current level descriptor wording and generate rewording suggestions. Thirty speech and language therapists, working in a variety of settings and geographical locations, were invited to be part of the Delphi expert panel. Content analysis was used to evaluate participants' comments and develop consensus level descriptors. Consensus for acceptable wording was set at 80% agreement. Face validity was assessed using 5-point Likert scales. Results: Nineteen expert speech and language therapists (median experience 18 years) completed round one; 15 out of 19 completed round two. Level descriptor rating reached 80% agreement in two rounds. Additionally, 93% of participants agreed the scale would accurately capture change in their setting, with 87% likely to use the scale in practice. Interpretation: This study has produced agreed wording for a functional measure of eating and drinking activity suitable for use with paediatrics feeding disorders, regardless of disease aetiology, presentation, age, or setting. Potential for widespread use is supported. Further evaluation of the tool's reliability and validity is required

The PD COMM trial: A protocol for the process evaluation of a randomised trial assessing the effectiveness of two types of SLT for people with Parkinson's disease

BACKGROUND: The PD COMM trial is a phase III multi-centre randomised controlled trial whose aim is to evaluate the effectiveness and cost-effectiveness of two approaches to speech and language therapy (SLT) compared with no SLT intervention (control) for people with Parkinson's disease who have self-reported or carer-reported problems with their speech or voice. Our protocol describes the process evaluation embedded within the outcome evaluation whose aim is to evaluate what happened at the time of the PD COMM intervention implementation and to provide findings that will assist in the interpretation of the PD COMM trial results. Furthermore, the aim of the PD COMM process evaluation is to investigate intervention complexity within a theoretical model of how the trialled interventions might work best and why. METHODS/DESIGN: Drawing from the Normalization Process Theory and frameworks for implementation fidelity, a mixed method design will be used to address process evaluation research questions. Therapists' and participants' perceptions and experiences will be investigated via in-depth interviews. Critical incident reports, baseline survey data from therapists, treatment record forms and home practice diaries also will be collected at relevant time points throughout the running of the PD COMM trial. Process evaluation data will be analysed independently of the outcome evaluation before the two sets of data are then combined. DISCUSSION: To date, there are a limited number of published process evaluation protocols, and few are linked to trials investigating rehabilitation therapies. Providing a strong theoretical framework underpinning design choices and being tailored to meet the complex characteristics of the trialled interventions, our process evaluation has the potential to provide valuable insight into which components of the interventions being delivered in PD COMM worked best (and what did not), how they worked well and why

The use of an HEPA respirator in combating SARS

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Evaluation of anti-oxidant capacity of root of Scutellaria baicalensis Georgi, in comparison with roots of polygonum multiflorum thunb and Panax ginseng CA Meyer

Author name used in this publication: Jian-Hong WuAuthor name used in this publication: Alice Lai-Shan AuAuthor name used in this publication: Peter Hoi-Fu Yu2009-2010 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Automated detection of mild cognitive impairment and dementia from voice recordings: A natural language processing approach

INTRODUCTION: Automated computational assessment of neuropsychological tests would enable widespread, cost-effective screening for dementia. METHODS: A novel natural language processing approach is developed and validated to identify different stages of dementia based on automated transcription of digital voice recordings of subjects' neuropsychological tests conducted by the Framingham Heart Study (n = 1084). Transcribed sentences from the test were encoded into quantitative data and several models were trained and tested using these data and the participants' demographic characteristics. RESULTS: Average area under the curve (AUC) on the held-out test data reached 92.6%, 88.0%, and 74.4% for differentiating Normal cognition from Dementia, Normal or Mild Cognitive Impairment (MCI) from Dementia, and Normal from MCI, respectively. DISCUSSION: The proposed approach offers a fully automated identification of MCI and dementia based on a recorded neuropsychological test, providing an opportunity to develop a remote screening tool that could be adapted easily to any language.AG054156 - NIA NIH HHS; RF1 AG062109 - NIA NIH HHS; AG049810 - NIA NIH HHS; U19 AG068753 - NIA NIH HHS; HHSN268201500001I - NHLBI NIH HHS; R01 AG016495 - NIA NIH HHS; UL54 TR004130 - NIH HHS; R01 GM135930 - NIGMS NIH HHS; RF1 AG072654 - NIA NIH HHS; AARG-NTF-20-643020 - Alzheimer's Association; R21-CA253498 - NIH HHS; AG033040 - NIA NIH HHS; AG068753 - NIA NIH HHS; R01-HL159620 - NIH HHS; AG016495 - NIA NIH HHS; R01 GM135930 - NIH HHS; AG008122 - NIA NIH HHS; R01 AG033040 - NIA NIH HHS; R56 AG062109 - NIA NIH HHS; AG062109 - NIA NIH HHS; CCF-2200052 - National Science Foundation; IIS-1914792 - National Science Foundation; DMS-1664644 - National Science FoundationAccepted manuscrip

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.published_or_final_versio

The transition to next generation sequencing from conventional sanger sequencing for breast cancer genetic study

Conference Theme: Cutting edge with integrative collaboration!Oral Presentation 4 - Detection and Diagnosis & Epidemiology & Supportive Care: no. OP4-1BACKGROUND/PURPOSE: The incidence of breast cancer is on the rise in Asia including Hong Kong. 40% of the breast cancer patients are diagnosed before age of 50 in Hong Kong. From clinical aspect, it is important to distinguish patients with inherited predis-position to breast cancer from sporadic cases, particularly in early-onset patients (<45 years old). BRCA1/2 have been widely investigated and frequently implicated in familial predisposition to breast cancer. Conventional Sanger sequencing has long been used and …published_or_final_versio

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Effect of Schistosomiasis and Soil-Transmitted Helminth Infections on Physical Fitness of School Children in Côte d'Ivoire

The burden of parasitic worm infections is considerable, particularly in developing countries. It is acknowledged that parasitic worm infections negatively impact on children's school performance and physical development. A deeper understanding of these linkages is important for updating burden of disease measures. We investigated the relationship between worm infection status and physical fitness of 156 school children from Côte d'Ivoire and controlled for potential confounding of Plasmodium infection (the causative agent of malaria) and environmental parameters (temperature and humidity). Children were diagnosed for parasitic worm and Plasmodium infections, examined by a physician, and participated in a 20 m shuttle run test to assess their maximal oxygen uptake (VO2 max) as a proxy for physical fitness. Most of the children had parasitic worms and a Plasmodium infection. Nevertheless, their physical fitness was excellent (average VO2 max: 52.7 ml kg−1 min−1). The level of VO2 max was only influenced by sex and age, but not by parasitic worms and Plasmodium infections. In future studies, the dynamics of children's physical performance should be assessed before and after control interventions, including the assessment of blood hemoglobin, hematocrit, and nutritional indicators to determine whether physical fitness in worm- and Plasmodium-infected individuals can be further improved