OCBE newsletter, April 2025

Welcome to the OCBE newsletter! This month, we showcase our recent publications on environmental exposures and cancer risk, drug repurposing, bacterial DNA sequencing and much more.

Publications

This study is the first to directly compare fetal scalp blood sample (FBS) lactate and ST analysis (STAN) in detecting adverse neonatal outcomes in singleton pregnancies. The findings reveal that STAN has higher sensitivity, while FBS lactate demonstrates higher specificity for the main outcome (umbilical cord artery pH ≤ 7.10). Thus, these results do not support the preference of one fetal surveillance system over the other.

 

The knockoff filter is a very popular approach for controlling FDR in high-dimensional regression problems, but it relies on pretty strict assumptions. The mirror statistic has been suggested as an alternative with less strict assumptions, but it is based on data splitting. In this paper, we suggest replacing the data splitting step with an outcome randomization step, leading to higher power and a computationally more efficient procedure.

 

Patients with substance use disorders are understudied. High quality information from various health registries in Norway and a clinical questionnaire was merged in this study. Post-selection inference was performed to account for data exploration in the model-selection and search for important factors associated with self-harm among those who committed suicide in this patient group.

 

Occupational exposures and kidney cancer in offshore petroleum workers, including investigation of components of healthy worker survivor bias.

 

Development of a Bayesian Belief Network model to quantify cardiovascular disease risk in individuals with type 1 diabetes. A paper from the Warifa project, a Horizon 2020 proof-of-concept project.

 

We take a functional output prediction approach, in which full, continuous dose-response combination surfaces are predicted for each drug combination on the cell lines.  We provide thorough experimental analysis of comboKR 2.0 with three real-word datasets within various challenging experimental settings, including cases where drugs or cell lines have not been encountered in the training data.

 

We found positive exposure-response associations between low-level benzene exposure and CRC risk in offshore petroleum workers, adding to the emerging evidence that benzene can be associated with solid tumors including lung and bladder.

 

  • Sergio Arredondo-Alonso, Anna K. Pöntinen, João Alves Gama, Rebecca A. Gladstone, Klaus Harms, Gerry Tonkin-Hill, Harry A. Thorpe, Gunnar S. Simonsen, Norwegian E. coli BSI Study Group, Ørjan Samuelsen, Pål J. Johnsen, Jukka Corander. Plasmid-driven strategies for clone success in Escherichia coli. Nature Communications. 2025 Apr 3;16(1):2921.

This is the first study to investigate population-wide DNA variation in both chromosomes and plasmids in a bacterial species (E. coli), using large-scale long-read sequencing with Oxford Nanopore Technnology. We established timelines of plasmid-driven emergence and expansion of multiple lineages of E. coli that have become pandemic in causing bloodstream infections. We further estimated population distribution of bacteriocin-producing genes (antimicrobial peptides) and used in vitro screening to show that the most successful plasmid-borne bacteriocins are able to inhibit all multi-drug resistant lineages of E. coli that are endemically circulating in Norway at high population frequencies. Our study facilitates developing novel strategies against opportunistic pathogens and serves as a pioneering high-resolution genome data resource for the research community.

 

  • Wenxin Wan, Susan Peters, Lützen Portengen, Ronnie Babigumira, Jo Steinson Stenehjem, David Richardson, and Roel Vermeulen. Response to “Comment on ‘Occupational Benzene Exposure and Lung Cancer in Human Studies: A Systematic Review and Meta-Analysis’”. Environmental Health Perspectives. 2025 Mar 13.

 

We performed functional phenotyping of CLL cells from patients enrolled in two clinical trials with umbralisib, administered either as a monotherapy (NCT02742090, n=55) or in combination with the BTK inhibitor acalabrutinib (NCT04624633, n=12). Functional phenotyping reveals differential cellular responses to umbralisib treatment in responders and non-responders; predicts treatment response of individual CLL patients; and suggests alternative treatment options for the non-responders.

 

  • Ziaurrehman Tanoli, Adrià Fernández-Torras, Umut Onur Özcan, Aleksandr Kushnir, Kristen Michelle Nader, Yojana Gadiya, Laura Fiorenza, Aleksandr Ianevski, Markus Vähä-Koskela, Mitro Miihkinen, Umair Seemab, Henri Leinonen, Brinton Seashore-Ludlow, Marianna Tampere, Adelinn Kalman, Flavio Ballante, Emilio Benfenati, Gary Saunders, Swapnil Potdar, Ismael Gómez García, Ricard García-Serna, Carmine Talarico, Andrea Rosario Beccari, Wesley Schaal, Andrea Polo, Susan Costantini, Enrico Cabri, Marc Jacobs, Jani Saarela, Alfredo Budillon, Ola Spjuth, Päivi Östling, Henri Xhaard, Jordi Quintana, Jordi Mestres, Philip Gribbon, Anton E. Ussi, Donald C. Lo, Martin de Kort, Krister Wennerberg, Maddalena Fratelli, Jordi Carreras-Puigvert, Tero Aittokallio. Computational drug repurposing: approaches, evaluation of in silico resources and case studies. Nature Reviews Drug Discovery. 2025 Mar 18:1-22.

We overview computational approaches to drug repurposing based on a comprehensive survey of available in silico resources using a purpose-built drug repurposing ontology that classifies the resources into hierarchical categories and provides application-specific information. We also present an expert evaluation of selected resources and three drug repurposing case studies implemented within the Horizon Europe REMEDi4ALL project to demonstrate the practical use of the resources.

Published Apr. 21, 2025 10:55 PM - Last modified Aug. 24, 2026 1:42 PM
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