Many cancer networks are failing to improve services.
Ontology highlight
ABSTRACT:
SUBMITTER: Mayor S
PROVIDER: S-EPMC1352042 | biostudies-literature | 2006 Jan
REPOSITORIES: biostudies-literature
Publications
Many cancer networks are failing to improve services.
BMJ (Clinical research ed.) 20060101 7535
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Project description:BackgroundAlternative splicing is a ubiquitous gene regulatory mechanism that dramatically increases the complexity of the proteome. However, the mechanism for regulating alternative splicing is poorly understood, and study of coordinated splicing regulation has been limited to individual cases. To study genome-wide splicing regulation, we integrate many human RNA-seq datasets to identify splicing module, which we define as a set of cassette exons co-regulated by the same splicing factors.ResultsWe have designed a tensor-based approach to identify co-splicing clusters that appear frequently across multiple conditions, thus very likely to represent splicing modules - a unit in the splicing regulatory network. In particular, we model each RNA-seq dataset as a co-splicing network, where the nodes represent exons and the edges are weighted by the correlations between exon inclusion rate profiles. We apply our tensor-based method to the 38 co-splicing networks derived from human RNA-seq datasets and indentify an atlas of frequent co-splicing clusters. We demonstrate that these identified clusters represent potential splicing modules by validating against four biological knowledge databases. The likelihood that a frequent co-splicing cluster is biologically meaningful increases with its recurrence across multiple datasets, highlighting the importance of the integrative approach.ConclusionsCo-splicing clusters reveal novel functional groups which cannot be identified by co-expression clusters, particularly they can grant new insights into functions associated with post-transcriptional regulation, and the same exons can dynamically participate in different pathways depending on different conditions and different other exons that are co-spliced. We propose that by identifying splicing module, a unit in the splicing regulatory network can serve as an important step to decipher the splicing code.
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Project description:BackgroundLung cancer is the most common cause of cancer death in the UK resulting in 21% of all cancer deaths. In 2016, local lung cancer surgery services required improvement due to under-representation in cancer resections and resource scarcity during the pandemic, which affected critical care bed availability and extended postoperative stays. The aim of this service improvement was to increase the number of lung cancer resection; develop minimally invasive techniques and reduce the use of Critical Care Unit beds by 35% (a subsequent goal).MethodsA five-year plan, guided by Kotter's 8-step change model, was initiated to address these issues. This model promotes sustainable change by setting clear goals, effective communication, and stakeholder involvement. Initial changes included hiring a thoracic surgeon experienced in uniportal video assisted thoracoscopy and enhanced recovery protocols. The team grew to three thoracic surgeons by 2020. The service increased operating theatre days and adopted new postoperative practices to reduce complications and hospital stays. Lung Cancer Multidisciplinary Team Meetings were consistently covered by thoracic surgeons, ensuring comprehensive care. Data on surgical activity were collected from departmental databases and national audits, with internal audits conducted regularly. Statistical significance was tested using chi-square tests with P values <0.05.ResultsThe number of surgical procedures more than doubled, with primary lung cancer resections increasing nearly three-fold from 12.8% to 29.8% over six years. Postoperative complications and mortality rates remained low. Critical care bed usage dropped significantly during the pandemic, with new protocols enabling safe recovery in general surgical areas.ConclusionsThe successful expansion of thoracic surgical services was attributed to the dedicated minimally invasive surgeons, enhanced recovery measures, and skilled staff. The change model facilitated efficient and dynamic progress. With the introduction of lung cancer screening programs, the demand for surgical services is expected to rise. The effective change model will be re-applied to meet this demand. The organizational change model, focused on patients and staff, achieved sustained quality improvement in lung cancer care despite challenging conditions like the coronavirus disease 2019 pandemic.
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