The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment.

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An atlas of genetic correlations across human diseases and traits.

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

FPGA implementation of high-speed tunable IIR band pass notch filter for identification of hot-spots in protein

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Hardware Implementation of Image and Video Watermarking for Ownership Verification

Utility companies are an integral part of the smart grid, providing consumers with a broad range of energy management programs. The quality of service is based on the measurements obtained from smart metering infrastructures, which can further be improved by sensing at finer resolutions. However, sensing at higher resolutions poses serious challenges both in terms of storage and communication overload due to overgrowing traffic. Compressive sensing is a data compression technique that accounts for the sparsity of electricity consumption pattern in a transformation basis and achieves subNyquist compression. To the best of the authors’ knowledge, this is the first study to use the semi-tensor product (STP) for compressed sensing (CS) of power consumption data in the smart grid. In contrast to the conventional CS, the proposed approach has the advantage of reducing the dimension of the sensing matrix needed to sense the signal, thereby significantly lowering the storage requirements. In this regard, we present a comparative study highlighting the difference in compression performance with the conventional CS and STP based CS, where the transformation basis used is Haar and Hankel. We present the results on three publicly available datasets at different sampling rates and outline the key findings of the study.

Storage Constrained Smart Meter Sensing using Semi-Tensor Product

Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer

Though systemic chemotherapy is the standard of care for the treatment of unresectable metastatic colorectal cancer, new drug delivery platforms are needed to mitigate the associated toxicities. The aim of this study was to develop and evaluate a liposome formulation that delivers oxaliplatin under magnetic field stimulus in a rat model of colorectal liver metastases. The drug delivery platform was synthesized by encapsulating iron oxide nanocubes and oxaliplatin in sterically stabilized polyethylene glycol (PEG)-coated liposomes of ~140 nm size. Magnetic properties and efficacy of drug release were determined by exposing the liposomes to an alternating magnetic field (AMF). In vitro efficacy of the liposomes was tested by performing viability assay on rat colorectal liver metastasis cell line (CC-531 cell line). For in vivo studies, rats implanted with CC-531 cells were divided into various groups and the efficacy of systemically delivered oxaliplatin was compared to localized and triggered delivery. Localized delivery and triggered release of drug was imaged by quantitative magnetic resonance and optical imaging methods. The rats were euthanized after 3 weeks, tumors harvested and HE 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4105.

Amit Joshi

Papers

FPGA implementation of high-speed tunable IIR band pass notch filter for identification of hot-spots in protein

Hardware Implementation of Image and Video Watermarking for Ownership Verification

Storage Constrained Smart Meter Sensing using Semi-Tensor Product

Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer

Abstract 4105: Localized and triggered release of oxaliplatin for the treatment of colorectal liver metastasis