A5062257210- Computational Drug Discovery Methods
- Viral-associated cancers and disorders
- Service and Product Innovation
- Adipose Tissue and Metabolism
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Biosimilars and Bioanalytical Methods
- Customer Service Quality and Loyalty
- Mitochondrial Function and Pathology
- Lymphoma Diagnosis and Treatment
- Health Systems, Economic Evaluations, Quality of Life
- Respiratory viral infections research
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Quality and Supply Management
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- Renal and related cancers
- Animal Genetics and Reproduction
- Gene expression and cancer classification
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- Product Development and Customization
- RNA modifications and cancer
- Mathematical Biology Tumor Growth
Wellcome Sanger Institute
2016-2025
Advanced Engineering Services (Japan)
2013-2014
Cranfield University
2006-2013
Howard Hughes Medical Institute
2012
Aston University
2011
Alterations in cancer genomes strongly influence clinical responses to treatment and many instances are potent biomarkers for response drugs. The Genomics of Drug Sensitivity Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource information on drug sensitivity cells molecular markers response. Data freely available without restriction. GDSC currently contains data almost 75 000 experiments, describing 138 anticancer drugs across 700 cell lines. To identify response,...
A Product-Service System (PSS) is an integrated combination of products and services. This Western concept embraces a service-led competitive strategy, environmental sustainability, the basis to differentiate from competitors who simply offer lower priced products. paper aims report state-of-the-art PSS research by presenting clinical review literature currently available on this topic. The classified major outcomes each study are addressed analysed. On basis, defines concept, reports its...
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature cancer. Using this information to guide development and application therapies in clinic is challenging. Here, we report how cancer-driven alterations identified 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, gene expression) can be mapped onto 1,001 molecularly annotated human cell lines correlated with sensitivity 265 drugs. We find...
Purpose The purpose of this paper is to report the state‐of‐the‐art servitization by presenting a clinical review literature currently available on topic. aims define concept, its origin, features and drivers give examples adoption along with future research challenges. Design/methodology/approach In determining scope study, focus articles that are central relevant within wider manufacturing context. methodology consists identifying publication databases, searching these using wide range key...
Purpose This paper aims to explore practices and technologies successfully servitised manufacturers employ in the delivery of advanced services.
The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection patient-derived tumor xenografts (PDTXs), which the morphological molecular characteristics originating are preserved through passaging mouse. An integrated platform combining vivo maintenance these PDTXs along with short-term cultures PDTX-derived cells (PDTCs) was optimized. Remarkably, genomic clonal architecture present cancers mostly upon...
Purpose This paper aims to present a framework that will help manufacturing firms configure their internal production and support operations enable effective efficient delivery of products closely associated services. Design/methodology/approach First, the key definitions literature sources directly with servitization are established. Then, theoretical categorises characteristics manufacturer's strategy is developed this populated using both evidence from extant empirical data. Findings The...
Purpose – The servitization of manufacturing is a diverse and complex field research interest. purpose this paper to provide an integrative organising lens for viewing the various contributions knowledge production from those communities addressing servitization. To achieve this, aims set out address two principal questions, namely where are stocks flows amongst communities? And what generic concerns being addressed by these Design/methodology/approach Using evidenced-based approach, authors...
Abstract Combinations of anti-cancer drugs can overcome resistance and provide new treatments 1,2 . The number possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active the tissues molecular contexts in which they are most effective accelerate development combination treatments. Here we evaluate potency efficacy 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast,...
Abstract Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic, and transcriptomic landscape primary tumor including point mutations, copy number alterations, mutational signatures. Karyotyping confirmed polyclonality reflecting clonal architecture tumor. Furthermore, subclones underwent...
Abstract CRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary adequately represent heterogeneity human cancers and assemble comprehensive map genetic vulnerabilities. Here, we integrated two largest public independent date (at Broad Sanger institutes) by assessing, comparing, selecting methods...
The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted identification new cancer biomarkers. Here, proteomes 949 cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence cell-type post-transcriptional modifications. Integrating multi-omics, drug response, CRISPR-Cas9 gene essentiality screens with deep...
Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities functionally map genetic vulnerabilities. Here, we construct a second-generation of dependencies by annotating 930 multi-omic analyze relationships between molecular markers derived from CRISPR-Cas9 screens. We identify dependency-associated expression beyond driver genes, observe many addiction driven gain rather than...
Purpose The purpose of this study is to examine a buyer's adoption servitization and the associated implications for relationships with its suppliers. Design/methodology/approach authors use case approach tripartite relationship between manufacturing company two paper explores perspectives employees on multiple organisational levels, collects evidence both sides relationship. template analysis utilising Cannon Perreault's connectors framework analyse data. Findings There are overarching...
In vitro cancer cell cultures are facile experimental models used widely for research and drug development. Many lines available efforts ongoing to derive new representing the histopathological molecular diversity of tumours. Cell have been generated by multiple laboratories over decades consequently their annotation is incomplete inconsistent. Furthermore, relationships between many patient-matched derivative lost, accessing information datasets time-consuming difficult. Here, we describe...
Purpose The debate about services‐led competitive strategies continues to grow, with much interest emerging around the differing practices between production and servitized operations. purpose of this paper is contribute discussion by investigating vertical integration practice (in particular micro‐vertical integration, otherwise known as supply chain position) manufacturers who are successful in their adoption servitization. Design/methodology/approach To achieve authors have investigated a...
Purpose – This “research note” sets out to fuel the debate around practices and technologies within operations that are critical success with servitization. It presents a study of four companies which delivering advanced services reports on organisation skill-sets people these. Design/methodology/approach has been case-based research at manufacturers leading in their delivery services. Findings describes desirable behaviour front-line service delivery, identifies supporting skill-sets, how...
CRISPR genetic screens in cancer cell models are a powerful tool to elucidate oncogenic mechanisms and identify promising therapeutic targets. The Project Score database (https://score.depmap.sanger.ac.uk/) uses genome-wide CRISPR-Cas9 dropout screening data hundreds of highly annotated genes required for fitness prioritize novel oncology currently allows users investigate the effect 18 009 tested across 323 models. Through interactive interfaces, can by selecting specific gene, model or...
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)n dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR-Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These compounds selectively suppressed model growth vitro...
Abstract Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible is vast be context-specific. Systematic screens identify clinically relevant, actionable in defined patient subtypes. We present data 109 anticancer from AstraZeneca's oncology small molecule portfolio screened 755 pan-cancer cell lines. Combinations were a 7 × concentration matrix, with more than 4 million measurements sensitivity, producing an...
Integrated vehicle health management (IVHM) is a collection of data relevant to the present and future performance system its transformation into information can be used support operational decisions. This design operation concept embraces an integration sensors, communication technologies, artificial intelligence provide vehicle-wide abilities diagnose problems recommend solutions. article aims report state-of-the-art IVHM research by presenting systematic review literature. The literature...