Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer

PURPOSE Circulating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here, we monitored ctDNA to detect clinically actionable alterations during treatment of high-grade serous ovarian cancer, the most common and aggressive form of epithelial ovarian cancer with a 5-year survival rate of 43%.PATIENTS AND METHODS We implemented a clinical ctDNA workflow to detect clinically actionable alterations in more than 500 cancer-related genes. We applied the workflow to a prospective cohort consisting of 78 ctDNA samples from 12 patients with high-grade serous ovarian cancer before, during, and after treatment. These longitudinal data sets were analyzed using our open-access ctDNA-tailored bioinformatics analysis pipeline and in-house Translational Oncology Knowledgebase to detect clinically actionable genomic alterations. The alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.RESULTS Our results show good concordance of mutations and copy number alterations in ctDNA and tumor samples, and alterations associated with clinically available drugs were detected in seven patients (58%). Treatment of one chemoresistant patient was changed on the basis of detection of ERBB2amplification, and this ctDNA-guided decision was followed by significant tumor shrinkage and complete normalization of the cancer antigen 125 tumor marker.CONCLUSION Our results demonstrate a proof of concept for using ctDNA to guide clinical decisions. Furthermore, our results show that longitudinal ctDNA samples can be used to identify poor-responding patients after first cycles of chemotherapy. We provide what we believe to be the first comprehensive, open-source ctDNA workflow for detecting clinically actionable alterations in solid cancers. (C) 2019 by American Society of Clinical Oncolog

Anduril 2: Upgraded large-scale data integration framework

aSummary: Anduril is an analysis and integration framework that facilitates the design, use, parallelization and reproducibility of bioinformatics workflows. Anduril has been upgraded to use Scala for pipeline construction, which simplifies software maintenance, and facilitates design of complex pipelines. Additionally, Anduril's bioinformatics repository has been expanded with multiple components, and tutorial pipelines, for next-generation sequencing data analysis.Peer reviewe

Preparing construction supply chains for blockchain technology:An investigation of its potential and future directions

Blockchain, a peer-to-peer, controlled, distributed database structure, has the potential to profoundly affect current business transactions in the construction industry through smart contracts, cryptocurrencies, and reliable asset tracking. The construction industry is often criticized for being slow in embracing emerging technologies and not effectively diffusing them through its supply chains. Often, the extensive fragmentation, traditional procurement structures, destructive competition, lack of collaboration and transparency, low-profit margins, and human resources are shown as the main culprits for this. As blockchain technology makes its presence felt strongly in many other industries like finance and banking, this study investigates the preparation of construction supply chains for blockchain technology through an explorative analysis. Empirical data for the study were collected through semistructured interviews with 17 subject experts. Alongside presenting a strengths, weaknesses, opportunities, and threats analysis (SWOT), the study exhibits the requirements for and steps toward a construction supply structure facilitated by blockchain technology

Towards a project theory: Theoretical contents of project management in 9 industry sectors

This paper reports upon articles on project management and their contents from the literatures of 9 industry sectors that recognize project management as a theoretical or practical field. The paper answers to: What are the theoretical and theme contents of project management in existing research in various sectors?, and; What are the commonalities and differences across sectors? We use bibliometric and qualitative analysis to identify sector-specific theoretical and theme contents, using data from the ISI Web of Science journal databases for 1986-2009, basing our analysis on 2,354 project management articles in altogether 564 journals. This work contributes to existing research by recognizing common orientations in 9 different sectors, as well as differences across sectors. The results are useful for understanding the cross-disciplinary nature of project management, and how the contents of project management are fragmented into several sector-specific paradigms, and how project management paradigm is systemically adopted across certain sectors