Eivind Hovig

• Akdeniz, Bayram Cevdet ; Frei, Oleksandr; Hagen, Espen; Filiz, Tahir Tekin; Karthikeyan, Sandeep & Pasman, Joëlle [Show all 18 contributors for this article] (2024). COSGAP: COntainerized Statistical Genetics Analysis Pipelines. Bioinformatics Advances. ISSN 2635-0041. 4(1). doi: 10.1093/bioadv/vbae067.
• Møller, Pål; Haupt, Saskia; Ahadova, Aysel; Kloor, Matthias; Sampson, Julian R. & Sunde, Lone [Show all 29 contributors for this article] (2024). Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 22(1). doi: 10.1186/s13053-024-00279-3.
• Edsjö, Anders; Russnes, Hege Elisabeth Giercksky; Lehtiö, Janne; Tamborero, David; Hovig, Eivind & Stenzinger, Albrecht [Show all 65 contributors for this article] (2024). High-throughput molecular assays for inclusion in personalised oncology trials – State-of-the-art and beyond. Journal of Internal Medicine. ISSN 0954-6820. 295(6), p. 785–803. doi: 10.1111/joim.13785.
• Reppe, Sjur; Gundersen, Sveinung; Sandve, Geir Kjetil Ferkingstad; Wang, Yunpeng; Andreassen, Ole & Medina-Gomez, Carolina [Show all 10 contributors for this article] (2024). Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease. International Journal of Molecular Sciences. ISSN 1661-6596. 25(10). doi: 10.3390/ijms25105554. Show summary

  Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n=84) from clinically well-characterized postmenopausal women (50 to 86 years) using microchips and RNA sequencing. Thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and their biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying overlap in single nucleotide polymorphisms (SNPs) within several genes encoding the aBMD and CVD associated transcripts.The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.

• Billingham, Lucinda; Brown, Lynn; Framke, Theodor; Greystoke, Alistair; Hovig, Eivind & Mathur, Siddharta [Show all 13 contributors for this article] (2023). Histology independent drug development – Is this the future for cancer drugs? Cancer Treatment Reviews. ISSN 0305-7372. 123. doi: 10.1016/j.ctrv.2023.102674.
• Rauluseviciute, Ieva; Riudavets-Puig, Rafael; Blanc-Mathieu, Romain; Castro Mondragon, Jaime Abraham; Ferenc, Katalin Terezia & Kumar, Vipin [Show all 20 contributors for this article] (2023). JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles. Nucleic Acids Research (NAR). ISSN 0305-1048. 52(D1), p. D174–D182. doi: 10.1093/nar/gkad1059. Full text in Research Archive Show summary

  JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release and 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing profiles and provided orthogonal support for 72 profiles from the previous release's UNVALIDATED collection. Altogether, the JASPAR 2024 update provides a 20% increase in CORE profiles from the previous release. A trimming algorithm enhanced profiles by removing low information content flanking base pairs, which were likely uninformative (within the capacity of the PFM models) for TFBS predictions and modelling TF-DNA interactions. This release includes enhanced metadata, featuring a refined classification for plant TFs’ structural DNA-binding domains. The new JASPAR collections prompt updates to the genomic tracks of predicted TF binding sites (TFBSs) in 8 organisms, with human and mouse tracks available as native tracks in the UCSC Genome browser. All data are available through the JASPAR web interface and programmatically through its API and the updated Bioconductor and pyJASPAR packages. Finally, a new TFBS extraction tool enables users to retrieve predicted JASPAR TFBSs intersecting their genomic regions of interest.

• Møller, Pål; Seppälä, Toni T.; Ahadova, Aysel; Crosbie, Emma J.; Holinski-Feder, Elke & Scott, Rodney [Show all 49 contributors for this article] (2023). Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 21(1), p. 1–12. doi: 10.1186/s13053-023-00263-3. Full text in Research Archive
• Akdeniz, Bayram Cevdet ; Mattingsdal, Morten; Dominguez-Valentin, Mev; Frei, Oleksandr; Shadrin, Alexey & Puustusmaa, Mikk [Show all 12 contributors for this article] (2023). A Breast Cancer Polygenic Risk Score Is Feasible for Risk Stratification in the Norwegian Population. Cancers. ISSN 2072-6694. 15(16). doi: 10.3390/cancers15164124. Full text in Research Archive
• Namløs, Heidi Maria; Khelik, Ksenia; Nakken, Sigve; Vodak, Daniel; Hovig, Eivind & Myklebost, Ola [Show all 8 contributors for this article] (2023). Chromosomal instability and a deregulated cell cycle are intrinsic features of high-risk gastrointestinal stromal tumours with a metastatic potential. Molecular Oncology. ISSN 1574-7891. 17(11), p. 2432–2450. doi: 10.1002/1878-0261.13514. Full text in Research Archive
• Nakken, Sigve; Gundersen, Sveinung; Bernal, Fabian Leonardo Martinez; Polychronopoulos, Dimitris; Hovig, Eivind & Wesche, Jørgen (2023). Comprehensive interrogation of gene lists from genome-scale cancer screens with oncoEnrichR. International Journal of Cancer. ISSN 0020-7136. 153(10), p. 1819–1828. doi: 10.1002/ijc.34666. Full text in Research Archive
• Kalyanasundaram, Sumana; Lefol, Yohan Pierre; Gundersen, Sveinung; Rognes, Torbjørn; Alsøe, Lene & Nilsen, Hilde [Show all 9 contributors for this article] (2023). hGSuite HyperBrowser: A web-based toolkit for hierarchical metadata-informed analysis of genomic tracks. PLOS ONE. ISSN 1932-6203. 18(7). doi: 10.1371/journal.pone.0286330. Full text in Research Archive
• Dominguez-Valentin, Mev; Haupt, Saskia; Seppälä, Toni T.; Sampson, Julian R.; Sunde, Lone & Bernstein, Inge [Show all 116 contributors for this article] (2023). Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database. EClinicalMedicine. ISSN 2589-5370. 58. doi: 10.1016/j.eclinm.2023.101909.
• Høye, Eirik; Dagenborg, Vegar Johansen; Kristensen, Annette Torgunrud; Lund-Andersen, Christin; Fretland, Åsmund Avdem & Lorenz, Susanne [Show all 13 contributors for this article] (2023). T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases. GigaScience. ISSN 2047-217X. 12. doi: 10.1093/gigascience/giad032. Full text in Research Archive
• Rodriguez-Varela, Ricardo; Moore, Kristjan H.S.; Ebenesersdottir, Sunna; Kilinc, Gulsah; Kjellström, Anna & Papmehl-Dufay, Ludvig [Show all 44 contributors for this article] (2023). The genetic history of Scandinavia from the Roman Iron Age to the present. Cell. ISSN 0092-8674. 186(1), p. 32–46. doi: 10.1016/j.cell.2022.11.024. Full text in Research Archive
• Akdeniz, Bayram Cevdet ; Frei, Oleksandr; Shadrin, Alexey; Vetrov, Dmitry; Kropotov, Dmitry & Dale, Anders [Show all 8 contributors for this article] (2022). Finemap-MiXeR: A variational Bayesian approach for genetic finemapping. bioRxiv. ISSN 2692-8205.
• Akdeniz, Bayram Cevdet ; Frei, Oleksandr; Hagen, Espen; Filiz, Tahir Tekin; Karthikeyan, Sandeep & Pasman, Joëlle [Show all 18 contributors for this article] (2022). COGEDAP: A COmprehensive GEnomic Data Analysis Platform. arXiv.org. ISSN 2331-8422.
• Hanes, Robert; Ayuda-Duran, Maria del Pilar; Rønneberg, Leiv; Nakken, Sigve; Hovig, Eivind & Zucknick, Manuela [Show all 7 contributors for this article] (2022). screenwerk: a modular tool for the design and analysis of drug combination screens. Bioinformatics. ISSN 1367-4803. 39(1). doi: 10.1093/bioinformatics/btac840. Full text in Research Archive
• Giliberto, Mariaserena; Miranda Santana, Leonardo; Holien, Toril; Misund, Kristine; Nakken, Sigve & Vodak, Daniel [Show all 12 contributors for this article] (2022). Mutational analysis and protein profiling predict drug sensitivity in multiple myeloma cell lines. Frontiers in Oncology. ISSN 2234-943X. 12:1040730, p. 1–14. doi: 10.3389/fonc.2022.1040730. Full text in Research Archive
• Zavaleta, Elizabeth; Solis, Nelly; Palacios, Maria Isabel; Zevallos-Escobar, Liz Elva; Corales, Edison Vasquez & Bazo-Alvarez, Juan Carlos [Show all 17 contributors for this article] (2022). Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru. Cancers. ISSN 2072-6694. 14(22), p. 1–13. doi: 10.3390/cancers14225603. Full text in Research Archive
• Møller, Pål; Seppälä, Toni; Dowty, James G.; Haupt, Saskia; Dominguez-Valentin, Mev & Sunde, Lone [Show all 157 contributors for this article] (2022). Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 20(1). doi: 10.1186/s13053-022-00241-1.
• Høye, Eirik; Fromm, Bastian; Böttger, Paul H.M.; Domanska, Diana; Kristensen, Annette Torgunrud & Lund-Andersen, Christin [Show all 13 contributors for this article] (2022). A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer. NAR Cancer. ISSN 2632-8674. 4(1), p. 1–13. doi: 10.1093/narcan/zcab051. Full text in Research Archive
• Ellingsen, Espen Basmo; Bounova, Gergana; Kerzeli, Iliana; Anzar, Irantzu; Simnica, Donjete & Aamdal, Elin [Show all 14 contributors for this article] (2022). Characterization of the T cell receptor repertoire and melanoma tumor microenvironment upon combined treatment with ipilimumab and hTERT vaccination. Journal of Translational Medicine. ISSN 1479-5876. 20(1). doi: 10.1186/s12967-022-03624-z. Full text in Research Archive Show summary

  Background This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment. Methods The trial was an open-label, single-center phase I/IIa study. Eligible patients had unresectable metastatic melanoma. Patients received up to 9 UV1 vaccinations and four ipilimumab infusions. Clinical responses were assessed according to RECIST 1.1. Patients were followed up for progression-free survival (PFS) and overall survival (OS). Whole-exome and RNA sequencing, and multiplex immunofluorescence were performed on the biopsies. T cell receptor (TCR) sequencing was performed on the peripheral blood and tumor tissues. Results Twelve patients were enrolled in the study. Vaccine-specific immune responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-γ gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-γ gene signature was detected in clinically responding patients. Conclusion Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors.

• Flobak, Åsmund; Skånland, Sigrid S; Hovig, Eivind; Tasken, Kjetil & Russnes, Hege Elisabeth Giercksky (2022). Functional precision cancer medicine: drug sensitivity screening enabled by cell culture models. TIPS - Trends in Pharmacological Sciences. ISSN 0165-6147. 43(11), p. 973–985. doi: 10.1016/j.tips.2022.08.009. Full text in Research Archive
• Alver, Tine Norman; Heintz, Karen Marie; Hovig, Eivind & Bøe, Sigurd (2022). Cooperative induction of receptor tyrosine kinases contributes to adaptive MAPK drug resistance in melanoma through the PI3K pathway. Cancer Reports. ISSN 2573-8348. doi: 10.1002/cnr2.1736. Full text in Research Archive Show summary

  emurafenib-induced drug resistance in melanoma has been linked to receptor tyrosinekinase (RTK) upregulation. The MITF and SOX10 genes play roles as master regulators ofmelanocyte and melanoma development. Here, we aimed to explore the complex mecha-nisms behind the MITF/SOX10-controlled RTK-induced drug resistance in melanoma. Toachieve this, we used a number of molecular techniques, including melanoma patient datafrom TCGA, vemurafenib-resistant melanoma cell lines, and knock-down studies. The mel-anoma cell lines were classified as proliferative or invasive based upon their MITF/AXLexpression activity. We measured the changeof expression activity for MITF/SOX10 andtheir receptor (AXL/ERBB3) and ligand (NRG1/GAS6) targets known to be involved inRTK-induced drug resistance after vemurafenib treatment. We find that melanoma celllines characterized as proliferative (high MITF low AXL), transform into an invasive (lowMITF, high AXL) cell state after vemurafenibresistance, indicating novel feedback loopsand advanced compensatory regulation mechanisms between the master regulators,receptors, and ligands involved in vemurafenib-induced resistance. Together, our data dis-close fine-tuned mechanisms involved in RTK-facilitated vemurafenibresistance that willbe challenging to overcome by using single drug targeting strategies against melanoma.

• Gopalakrishnan, Shyam; Ebenesersdottir, S.Sunna; Lundstrøm, Inge K.C.; Turner-Walker, Gordon; Moore, Kristjan H.S. & Luisi, Pierre [Show all 60 contributors for this article] (2022). The population genomic legacy of the second plague pandemic. Current Biology. ISSN 0960-9822. 32, p. 4743–4751. doi: 10.1016/j.cub.2022.09.023. Full text in Research Archive Show summary

  Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.

• Venizelos, Andreas; Engebrethsen, Christina; Deng, Wei; Geisler, Jürgen; Geisler, Stephanie & Iversen, Gjertrud Titlestad [Show all 18 contributors for this article] (2022). Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy. Genome Medicine. ISSN 1756-994X. 14, p. 1–18. doi: 10.1186/s13073-022-01090-2. Full text in Research Archive
• Ellingsen, Espen Basmo; Aamdal, Elin; Guren, Tormod Kyrre; Lilleby, Wolfgang; Brunsvig, Paal Fr. & Mangsbo, Sara M [Show all 11 contributors for this article] (2022). Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: Long-Term follow-up of three phase i clinical trials. Journal for ImmunoTherapy of Cancer (JITC). 10(5), p. 1–13. doi: 10.1136/jitc-2021-004345. Full text in Research Archive Show summary

  Background Therapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although telomerase is a near-universal tumor target, different treatment combinations applied across indications may affect the induced immune response. Three phase I/IIa clinical trials covering malignant melanoma, non-small cell lung cancer, and prostate cancer have been completed, with patients in follow-up for up to 8 years. Methods 52 patients were enrolled across the three trials. UV1 was given as monotherapy in the lung cancer trial and concurrent with combined androgen blockade in the prostate cancer trial. In the melanoma study, patients initiated ipilimumab treatment 1 week after the first vaccine dose. Patients were followed for UV1-specific immune responses at frequent intervals during vaccination, and every 6 months for up to 8 years in a follow-up period. Phenotypic and functional characterizations were performed on patient-derived vaccine-specific T cell responses. Results In total, 78.4% of treated patients mounted a measurable vaccine-induced T cell response in blood. The immune responses in the malignant melanoma trial, where UV1 was combined with ipilimumab, occurred more rapidly and frequently than in the lung and prostate cancer trials. In several patients, immune responses peaked years after their last vaccination. An in-depth characterization of the immune responses revealed polyfunctional CD4+ T cells producing interferon-γ and tumor necrosis factor-α on interaction with their antigen. Conclusion Long-term immunomonitoring of patients showed highly dynamic and persistent telomerase peptide-specific immune responses lasting up to 7.5 years after the initial vaccination, suggesting a plausible functional role of these T cells in long-term survivors. The superior immune response kinetics observed in the melanoma study substantiate the rationale for future combinatorial treatment strategies with UV1 vaccination and checkpoint inhibition for rapid and frequent induction of anti-telomerase immune responses in patients with cancer.

• Misund, Kristine; Hofste op Bruinink, Davine; Coward, Eivind; Hoogenboezem, Remco M.; Rustad, Even Holth & Sanders, Mathijs A. [Show all 16 contributors for this article] (2022). Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence. Leukemia. ISSN 0887-6924. 36(7), p. 1887–1897. doi: 10.1038/s41375-022-01597-y. Full text in Research Archive
• Fromm, Bastian; Høye, Eirik; Domanska, Diana; Zhong, Xiangfu; Aparicio-Puerta, Ernesto & Ovchinnikov, Vladimir [Show all 18 contributors for this article] (2022). MirGeneDB 2.1: toward a complete sampling of all major animal phyla. Nucleic Acids Research (NAR). ISSN 0305-1048. 50(D1), p. D204–D210. doi: 10.1093/nar/gkab1101. Full text in Research Archive
• Dominguez-Valentin, Mev; Plazzer, John-Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan & Jenkins, Mark A. [Show all 89 contributors for this article] (2021). No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study. Journal of Clinical Medicine. ISSN 2077-0383. 10(13), p. 1–12. doi: 10.3390/jcm10132856. Full text in Research Archive
• Seppälä, Toni T.; Dominguez-Valentin, Mev; Crosbie, Emma J.; Engel, Christoph; Aretz, Stefan & Macrae, Finlay [Show all 86 contributors for this article] (2021). Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report. European Journal of Cancer. ISSN 0959-8049. 148, p. 124–133. doi: 10.1016/j.ejca.2021.02.022.
• Gundersen, Sveinung; Boddu, Sanjay; Capella-Gutierrez, Salvador; Drabløs, Finn; Fernández, José M. & Kompova, Radmila [Show all 10 contributors for this article] (2021). Recommendations for the FAIRification of genomic track metadata. F1000 Research. ISSN 2046-1402. 10. doi: 10.12688/f1000research.28449.1. Full text in Research Archive
• Ellingsen, Espen Basmo; Mangsbo, Sara; Hovig, Eivind & Gaudernack, Gustav (2021). Telomerase as a Target for Therapeutic Cancer Vaccines and Considerations for Optimizing Their Clinical Potential. Frontiers in Immunology. ISSN 1664-3224. 12:682492, p. 1–15. doi: 10.3389/fimmu.2021.682492. Full text in Research Archive
• Pavlović, Milena; Scheffer, Lonneke; Motwani, Keshav; Kanduri, Chakravarthi; Kompova, Radmila & Vazov, Nikolay Aleksandrov [Show all 41 contributors for this article] (2021). The immuneML ecosystem for machine learning analysis of adaptive immune receptor repertoires. Nature Machine Intelligence. 3(11), p. 936–944. doi: 10.1038/s42256-021-00413-z.
• Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Bucher-Johannessen, Cecilie; Vinberg, Elina; Nordby, Jan Inge & Kangas, Harri [Show all 27 contributors for this article] (2021). The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants. BMC Cancer. ISSN 1471-2407. 21. doi: 10.1186/s12885-021-08640-8. Full text in Research Archive
• Nakken, Sigve; Saveliev, Vladislav; Hofmann, Oliver; Møller, Pål; Myklebost, Ola & Hovig, Eivind (2021). Cancer Predisposition Sequencing Reporter (CPSR): A flexible variant report engine for high-throughput germline screening in cancer. International Journal of Cancer. ISSN 0020-7136. p. 1–6. doi: 10.1002/ijc.33749. Full text in Research Archive Show summary

  The value of high-throughput germline genetic testing is increasingly recognized inclinical cancer care. Disease-associated germline variants in cancer patients areimportant for risk management and surveillance, surgical decisions and can also havemajor implications for treatment strategies since many are in DNA repair genes. Withthe increasing availability of high-throughput DNA sequencing in cancer clinics andresearch, there is thus a need to provide clinically oriented sequencing reports forgermline variants and their potential therapeutic relevance on a per-patient basis. Tomeet this need, we have developed the Cancer Predisposition Sequencing Reporter(CPSR), an open-source computational workflow that generates a structured reportof germline variants identified in known cancer predisposition genes, highlightingmarkers of therapeutic, prognostic and diagnostic relevance. A fully automated vari-ant classification procedure based on more than 30 refined American College ofMedical Genetics and Genomics (ACMG) criteria represents an integral part of theworkflow. Importantly, the set of cancer predisposition genes profiled in the reportcan be flexibly chosen from more than 40 virtual gene panels established by scientificexperts, enabling customization of the report for different screening purposes andclinical contexts. The report can be configured to also list actionable secondary vari-ant findings, as recommended by ACMG. CPSR demonstrates comparable sensitivityand specificity for the detection of pathogenic variants when compared to otheralgorithms in the field. Technically, the tool is implemented in Python/R, and is freelyavailable through Docker technology. Source code, documentation, example reportsand installation instructions are accessible via the project GitHub page: https://github.com/sigven/cpsr.

• Mattingsdal, Morten; Ebenesersdóttir, Sigríður Sunna; Moore, Kristjan H. S.; Andreassen, Ole Andreas; Hansen, Thomas F. & Werge, Thomas [Show all 12 contributors for this article] (2021). The genetic structure of Norway. European Journal of Human Genetics. ISSN 1018-4813. doi: 10.1038/s41431-021-00899-6. Full text in Research Archive
• Nakken, Sigve; Lilleby, Wolfgang; Switlyk, Marta Daniela; Knudsen, Karen E.; Lilleby, Oscar & Zhao, Sen [Show all 10 contributors for this article] (2021). The quandary of dna-based treatment assessment in de novo metastatic prostate cancer in the era of precision oncology. Journal of Personalized Medicine. 11(5), p. 1–18. doi: 10.3390/jpm11050330. Full text in Research Archive
• Aamdal, Elin; Inderberg, Else Marit ; Ellingsen, Espen Basmo; Rasch, Wenche; Brunsvig, Paal Fr. & Aamdal, Steinar [Show all 13 contributors for this article] (2021). Combining a universal telomerase based cancer vaccine with ipilimumab in patients with metastatic melanoma - Five-year follow up of a phase I/IIa trial. Frontiers in Immunology. ISSN 1664-3224. 12, p. 1–10. doi: 10.3389/fimmu.2021.663865. Full text in Research Archive
• Salgado, David; Béroud, Christophe; Armean, Irina M.; Baudis, Michael; Beltran, Sergi & Capella, Salvador [Show all 42 contributors for this article] (2020). The ELIXIR Human Copy Number Variations Community: Building bioinformatics infrastructure for research. F1000. ISSN 1759-796X. 9:1229, p. 1–15. doi: 10.12688/f1000research.24887.1.
• Dominguez-Valentin, Mev; Seppälä, Toni T.; Engel, Christoph; Aretz, Stefan; Macrae, Finlay & Winship, Ingrid [Show all 45 contributors for this article] (2020). Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database. Journal of Clinical Medicine. ISSN 2077-0383. 9(7). doi: 10.3390/jcm9072290.
• Wise, Jillian; Nakken, Sigve; Steen, Chloe Beate; Vodak, Daniel; Trøen, Gunhild & Johannessen, Bjarne [Show all 24 contributors for this article] (2020). Mutational dynamics and immune evasion in diffuse large B-cell lymphoma explored in a relapse-enriched patient series. Blood Advances. ISSN 2473-9529. 4(9), p. 1859–1866. doi: 10.1182/bloodadvances.2019001325. Show summary

  • Diagnostic and relapse diffuse large B-cell lymphoma (DLBCL) biopsies reveal increased mutational burden/loss of heterozygosity in HLA-A. • Serially sampled tumor biopsies provide insight into therapeutic targets and evolutionary divergence in relapsed/refractory DLBCL.

• Dominguez-Valentin, Mev; Crosbie, Emma J.; Engel, Christoph; Aretz, Stefan; MacRae, Finlay & Winship, Ingrid [Show all 88 contributors for this article] (2020). Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report. Genetics in Medicine. ISSN 1098-3600. p. 1–8. doi: 10.1038/s41436-020-01029-1. Full text in Research Archive
• Pace, Marta; Falappa, Matteo; Freschi, Andrea; Balzani, Edoardo; Berteotti, Chiara & Martire, Viviana Lo [Show all 13 contributors for this article] (2020). Loss of Snord116 impacts lateral hypothalamus, sleep, and food-related behaviors. JCI Insight. ISSN 2379-3708. 5(12), p. 1–18. doi: 10.1172/jci.insight.137495.
• Zhao, Sen; Agafonov, Oleg; Azab, Abdulrahman; Stokowy, Tomasz & Hovig, Eivind (2020). Accuracy and efficiency of germline variant calling pipelines for human genome data. Scientific Reports. ISSN 2045-2322. 10:20222, p. 1–12. doi: 10.1038/s41598-020-77218-4. Full text in Research Archive
• Olafsdottir, Elinborg J.; Borg, Åke; Jensen, Maj-Britt; Gerdes, Anne-Marie; Johansson, Anna L. V. & Barkardottir, Rosa B. [Show all 20 contributors for this article] (2020). Breast cancer survival in Nordic BRCA2 mutation carriers—unconventional association with oestrogen receptor status. British Journal of Cancer. ISSN 0007-0920. 123, p. 1608–1615. doi: 10.1038/s41416-020-01056-4.
• Lavelle, Timothy J; Alver, Tine Norman; Heintz, Karen Marie; Wernhoff, Patrik; Nygaard, Vegard & Nakken, Sigve [Show all 10 contributors for this article] (2020). Dysregulation of MITF Leads to Transformation in MC1R-Defective Melanocytes. Cancers. ISSN 2072-6694. 12(7), p. 1–20. doi: 10.3390/cancers12071719. Full text in Research Archive
• Ree, Anne Hansen; Nygaard, Vigdis; Pedersen, Kjetil Boye; Heinrich, Daniel; Dueland, Svein & Bergheim, Inger Riise [Show all 25 contributors for this article] (2020). Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer?the MetAction study. Acta Oncologica. ISSN 0284-186X. p. 1–10. doi: 10.1080/0284186X.2020.1742377. Full text in Research Archive
• Waaler, Jo; Mygland, Line; Tveita, Anders Aune; Strand, Martin Frank; Solberg, Nina & Olsen, Petter Angell [Show all 19 contributors for this article] (2020). Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models. Communications Biology. ISSN 2399-3642. 3. doi: 10.1038/s42003-020-0916-2. Full text in Research Archive
• Tolios, Alexander; De Las Rivas, Javier; Hovig, Eivind; Trouillas, Patrick; Scorilas, Andreas & Mohr, Thomas (2020). Computational approaches in cancer multidrug resistance research: Identification of potential biomarkers, drug targets and drug-target interactions. Drug resistance updates. ISSN 1368-7646. 48:100662, p. 1–15. doi: 10.1016/j.drup.2019.100662.
• Lund-Andersen, Christin; Nakken, Sigve; Nygård, Ståle; Fromm, Bastian; Aasheim, Lars Birger & Davidson, Ben [Show all 13 contributors for this article] (2019). Integrative genomic analysis of peritoneal malignant mesothelioma: Understanding a case with extraordinary chemotherapy response. Cold Spring Harbor Molecular Case Studies. ISSN 2373-2873. 5:a003566(2), p. 1–15. doi: 10.1101/mcs.a003566. Full text in Research Archive
• Pashov, Anastas; Shivarov, Velizar; Hadzhieva, Maya; Kostov, Victor; Ferdinandov, Dilyan & Heintz, Karen Marie [Show all 12 contributors for this article] (2019). Diagnostic Profiling of the Human Public IgM Repertoire With Scalable Mimotope Libraries. Frontiers in Immunology. ISSN 1664-3224. 10, p. 1–14. doi: 10.3389/fimmu.2019.02796.
• Dominguez-Valentin, Mev; Nakken, Sigve; Tubeuf, Hélène; Vodák, Daniel; Ekstrøm, Per Olaf & Nissen, Anke M. [Show all 15 contributors for this article] (2019). Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing. Scientific Reports. ISSN 2045-2322. 9:18555, p. 1–9. doi: 10.1038/s41598-019-54517-z. Full text in Research Archive
• Fromm, Bastian; Domanska, Diana Ewa; Høye, Eirik; Ovchinnikov, Vladimir; Kang, Wenjing & Aparicio-Puerta, Ernesto [Show all 13 contributors for this article] (2019). MirGeneDB 2.0: the metazoan microRNA complement . Nucleic Acids Research (NAR). ISSN 0305-1048. 48(D1), p. D132–D141. doi: 10.1093/nar/gkz885. Full text in Research Archive
• Della Valle, Adriana; Rossi, Benedito Mauro; Palmero, Edenir Inêz; Antelo, Marina; Vaccaro, Carlos Alberto & López-Köstner, Francisco [Show all 72 contributors for this article] (2019). A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries. European Journal of Cancer. ISSN 0959-8049. 119, p. 112–121. doi: 10.1016/j.ejca.2019.07.017.
• Dominguez-Valentin, Mev; Sampson, Julian R.; Seppälä, Toni T.; ten Broeke, Sanne W.; Plazzer, John-Paul & Nakken, Sigve [Show all 88 contributors for this article] (2019). Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in Medicine. ISSN 1098-3600. 22, p. 15–25. doi: 10.1038/s41436-019-0596-9. Full text in Research Archive
• Nygård, Ståle; Lingjærde, Ole Christian; Caldas, Carlos; Hovig, Eivind; Børresen-Dale, Anne-Lise & Helland, Åslaug [Show all 7 contributors for this article] (2019). PathTracer: High-sensitivity detection of differential pathway activity in tumours. Scientific Reports. ISSN 2045-2322. 9:16332, p. 1–8. doi: 10.1038/s41598-019-52529-3. Full text in Research Archive
• Dominguez-Valentin, Mev; Seppälä, Toni T.; Sampson, Julian R.; MacRae, Finlay; Winship, Ingrid & Evans, D. Gareth [Show all 43 contributors for this article] (2019). Survival by colon cancer stage and screening interval in Lynch syndrome: A prospective Lynch syndrome database report. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 17:28, p. 1–6. doi: 10.1186/s13053-019-0127-3.
• Seppälä, Toni T.; Ahadova, Aysel; Dominguez-Valentin, Mev; Macrae, Finlay; Evans, D. Gareth & Therkildsen, Christina [Show all 57 contributors for this article] (2019). Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; A prospective Lynch syndrome database report. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 17:8, p. 1–8. doi: 10.1186/s13053-019-0106-8.
• Ree, Anne Hansen; Nygaard, Vigdis; Russnes, Hege Elisabeth Giercksky; Heinrich, Daniel; Nygaard, Vegard & Johansen, Christin [Show all 13 contributors for this article] (2019). Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain. Cancer immunology research. ISSN 2326-6066. 7(5), p. 701–706. doi: 10.1158/2326-6066.CIR-18-0777. Full text in Research Archive
• Møller, Pål; Dominguez-Valentin, Mev; Rødland, Einar Andreas & Hovig, Eivind (2019). Causes for Frequent Pathogenic BRCA1 Variants Include Low Penetrance in Fertile Ages, Recurrent De-Novo Mutations and Genetic Drift. Cancers. ISSN 2072-6694. 11(2), p. 1–11. doi: 10.3390/cancers11020132.
• Kanduri, Srinivasa Kalyana Chakravarthi; Bock, Christoph; Gundersen, Sveinung; Hovig, Eivind & Sandve, Geir Kjetil (2019). Colocalization analyses of genomic elements: approaches, recommendations and challenges. Bioinformatics. ISSN 1367-4803. 35(9), p. 1615–1624. doi: 10.1093/bioinformatics/bty835. Full text in Research Archive
• Azab, Abdulrahman; Meling, Hein; Hovig, Eivind & Pursula, Antti (2018). Filesystem Front-end for Seamless Job Management in Sensitive Data e-Infrastructures and Cloud Federation. In Abe, Naoki; Liu, Huan; Hu, Xiaohua; Ahmed, Nesreen; Qiao, Mu; Song, Yang; Kossmann, Donald; Liu, Bing; Lee, Kisung; Tang, Jiliang; He, Jingrui & Saltz, Jeffrey (Ed.), 2018 IEEE International Conference on Big Data (Big Data), Seattle, 10-13 Dec. 2018. IEEE (Institute of Electrical and Electronics Engineers). ISSN 978-1-5386-5035-6. doi: 10.1109/BigData.2018.8622144.
• Vaccaro, Carlos Alberto; López‐Kostner, Francisco; Della Valle, Adriana; Palmero, Edenir Inêz; Rossi, Benedito Mauro & Antelo, Marina [Show all 69 contributors for this article] (2018). From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America. International Journal of Cancer. ISSN 0020-7136. doi: 10.1002/ijc.31920. Full text in Research Archive Show summary

  Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

• Møller, Pål; Seppälä, Toni T.; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paulo & Evans, D. Gareth [Show all 39 contributors for this article] (2018). Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut. ISSN 0017-5749. 67(7), p. 1306–1316. doi: 10.1136/gutjnl-2017-314057. Full text in Research Archive
• Tekle, Kidane M; Gundersen, Sveinung; Klepper, Kjetil; Bongo, Lars Ailo; Raknes, Inge Alexander & Li, Xiaxi [Show all 22 contributors for this article] (2018). Norwegian e-Infrastructure for Life Sciences (NeLS). F1000 Research. ISSN 2046-1402. 7:968. doi: 10.5256/f1000research.16472.r35600. Full text in Research Archive
• Ebenesersdóttir, Sigríður Sunna; Sandoval-Velasco, Marcela; Gunnarsdóttir, Ellen D.; Jagadeesan, Anuradha; Guðmundsdóttir, Valdís B. & Thordardóttir, Elísabet L. [Show all 30 contributors for this article] (2018). Ancient genomes from Iceland reveal the making of a human population. Science. ISSN 0036-8075. 360(6392), p. 1028–1032. doi: 10.1126/science.aar2625. Full text in Research Archive
• Dominguez Valentin, Mev; Evans, D. Gareth R.; Nakken, Sigve; Tubeuf, Hélène; Vodak, Daniel & Ekstrøm, Per Olaf [Show all 12 contributors for this article] (2018). Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 16:4, p. 1–14. doi: 10.1186/s13053-018-0086-0. Full text in Research Archive
• Dominguez Valentin, Mev; Nakken, Sigve; Tubeuf, Hélène; Vodak, Daniel; Ekstrøm, Per Olaf & Nissen, Anke M. [Show all 11 contributors for this article] (2018). Identification of genetic variants for clinical management of familial colorectal tumors. BMC Medical Genetics. ISSN 1471-2350. 19(1). doi: 10.1186/s12881-018-0533-9. Full text in Research Archive
• Vodak, Daniel; Lorenz, Susanne; Nakken, Sigve; Aasheim, Lars Birger; Holte, Harald & Bai, Baoyan [Show all 9 contributors for this article] (2018). Sample-Index Misassignment Impacts Tumour Exome Sequencing. Scientific Reports. ISSN 2045-2322. 8:5307, p. 1–6. doi: 10.1038/s41598-018-23563-4. Full text in Research Archive
• Birkeland, Einar Elvbakken; Zhang, Shan; Poduval, Deepak; Geisler, Jürgen; Nakken, Sigve & Vodak, Daniel [Show all 11 contributors for this article] (2018). Patterns of genomic evolution in advanced melanoma. Nature Communications. ISSN 2041-1723. 9:2665, p. 1–12. doi: 10.1038/s41467-018-05063-1. Full text in Research Archive
• Clancy, Trevor; dannenfelser, ruth; Troyanskaya, Olga G.; Malmberg, Karl-Johan; Hovig, Eivind & Kristensen, Vessela N. (2017). Bioinformatics approaches to profile the tumor microenvironment for immunotherapeutic discovery. Current pharmaceutical design. ISSN 1381-6128. 23(32), p. 4716–4725. doi: 10.2174/1381612823666170710154936. Full text in Research Archive Show summary

  In the microenvironment of a malignancy, tumor cells do not exist in isolation, but rather in a diverse ecosystem consisting not only of heterogeneous tumor-cell clones, but also normal cell types such as fibroblasts, vasculature, and an extensive pool of immune cells at numerous possible stages of activation and differentiation. This results in a complex interplay of diverse cellular signaling systems, where the immune cell component is now established to influence cancer progression and therapeutic response. It is experimentally difficult and laborious to comprehensively and systematically profile these distinct cell types from heterogeneous tumor samples in order to capitalize on potential therapeutic and biomarker discoveries. One emerging solution to address this challenge is to computationally extract cell-type specific information directly from bulk tumors. Such in silico approaches are advantageous because they can capture both the cell-type specific profiles and the tissue systems level of cell-cell interactions. Accurately and comprehensively predicting these patterns in tumors is an important challenge to overcome, not least given the success of immunotherapeutic drug treatment of several human cancers. This is especially challenging for subsets of closely related immune cell phenotypes with relatively small gene expression differences, which have critical functional distinctions. Here, we outline the existing and emerging novel bioinformatics strategies that can be used to profile the tumor immune landscape.

• Møller, Pål & Hovig, Eivind (2017). The BRCA2 variant c.68-7 T>A is associated with breast cancer. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 15(1). doi: 10.1186/s13053-017-0080-y.
• Rossi, Benedito Mauro; Palmero, Edenir Inêz; López-Kostner, Francisco; Sarroca, Carlos; Vaccaro, Carlos Alberto & Spirandelli, Florencia [Show all 37 contributors for this article] (2017). A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. BMC Cancer. ISSN 1471-2407. 17(623). doi: 10.1186/s12885-017-3599-4.
• Seppälä, Toni; Pylvänäinen, Kirsi; Evans, Dafydd Gareth; Järvinen, Heikki; Renkonen-Sinisalo, Laura & Bernstein, Inge [Show all 39 contributors for this article] (2017). Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols: A Prospective Lynch Syndrome Database report. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 15:18, p. 1–10. doi: 10.1186/s13053-017-0078-5. Full text in Research Archive
• Møller, Pål; Seppälä, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola & Evans, D. Gareth [Show all 38 contributors for this article] (2017). Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: A report from the prospective Lynch syndrome database. Gut. ISSN 0017-5749. 66(9), p. 1657–1664. doi: 10.1136/gutjnl-2016-311403. Full text in Research Archive

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• Przybyła, Weronika; Trøen, Gunhild; Lai, Xiaoran; Samarakoon, Pubudu Saneth; Kaveh, Fatemeh & Hovig, Eivind [Show all 8 contributors for this article] (2023). Comparative whole genome copy number analysis of disseminated tumor cells and the primary tumor in high-risk neuroblastoma.
• Akdeniz, Bayram Cevdet ; Bøen, Rune; Frei, Oleksandr; Hovig, Eivind; Andreassen, Ole & Sønderby, Ida Elken (2022). LARGE-SCALE ANALYSIS WITH SOFTWARE CONTAINERS IN ENIGMA-CNV–AN INTERNATIONAL WORKING GROUP TO STUDY RECURRENT COPY NUMBER VARIANTS AND BRAIN MEASURES. Neuropsychopharmacology, 2022.
• Akdeniz, Bayram Cevdet ; Mattingsdal, Morten; Dominguez Valentin, Mev; Frei, Oleksandr; Shadrin, Alexey & Puustusmaa, Mikk [Show all 11 contributors for this article] (2022). Implementation of polygenic risk score guided breast cancer prediction in Norwegian data. NSHG-PM 2022.
• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: the MoBaPsychGen_v1 pipeline.
• Tasken, Kjetil; Russnes, Hege Elisabeth Giercksky; Aas, Eline; Bjørge, Line; Blix, Egil Støre & Ahlquist, Terje C. [Show all 116 contributors for this article] (2022). A national precision cancer medicine implementation initiative for Norway. Nature Medicine. ISSN 1078-8956. 28(5), p. 885–887. doi: 10.1038/s41591-022-01777-4.
• Helland, Åslaug; Russnes, Hege Elisabeth Giercksky; Fagereng, Gro Live; Al-Shibli, Khalid Ibrahim; Andersson, Yvonne & Berg, Thomas [Show all 53 contributors for this article] (2022). Correction to: Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway (Journal of Translational Medicine, (2022), 20, 1, (225), 10.1186/s12967-022-03432-5). Journal of Translational Medicine. ISSN 1479-5876. 20(1). doi: 10.1186/s12967-022-03518-0.
• Helland, Åslaug; Russnes, Hege Elisabeth Giercksky; Fagereng, Gro Live; Al-Shibli, Khalid Ibrahim; Andersson, Yvonne & Berg, Thomas [Show all 53 contributors for this article] (2022). Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway. Journal of Translational Medicine. ISSN 1479-5876. 20(1), p. 1–11. doi: 10.1186/s12967-022-03432-5. Full text in Research Archive Show summary

  Background Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. Methods In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient’s tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like ‘admissible’ monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system.

• Dominguez-Valentin, Mev; Sampson, Julian R.; Møller, Pål; Seppälä, Toni T.; Plazzer, John-Paul & Nakken, Sigve [Show all 88 contributors for this article] (2021). Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum. International Journal of Cancer. ISSN 0020-7136. 148(2), p. 512–513. doi: 10.1002/ijc.33214.
• Kanduri, Chakravarthi; Sandve, Geir Kjetil Ferkingstad; Hovig, Eivind; De, Subhajyoti & Layer, Ryan (2021). Editorial: Genomic Colocalization and Enrichment Analyses. Frontiers in Genetics. ISSN 1664-8021. 11. doi: 10.3389/fgene.2020.617876.
• Stansberg, Christine; Hovig, Eivind; Willassen, Nils Peder & Jonassen, Inge (2021). Det er arbeidskrevende å gjøre data delbare! Khrono.no. ISSN 1894-8995.
• Dominguez-Valentin, Mev; Sampson, Julian R.; Seppälä, Toni T.; ten Broeke, Sanne W.; Plazzer, John-Paul & Nakken, Sigve [Show all 88 contributors for this article] (2020). Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (Genetics in Medicine, (2020), 22, 1, (15-25), 10.1038/s41436-019-0596-9). Genetics in Medicine. ISSN 1098-3600. 22(9). doi: 10.1038/s41436-020-0892-4.
• Møller, Pål; Dominguez-Valentin, Mev; Rødland, Einar Andreas & Hovig, Eivind (2020). Correction: Causes for frequent pathogenic brca1 variants include low penetrance in fertile ages, recurrent de-novo mutations and genetic drift (Cancers, (2019), 11, 132, 10.3390/cancers11020132). Cancers. ISSN 2072-6694. 12(2). doi: 10.3390/cancers12020410.
• Fromm, Bastian; Domanska, Diana; Høye, Eirik; Ovchinnikov, Vladimir; Kang, Wenjing & Aparicio-Puerta, Ernesto [Show all 13 contributors for this article] (2020). Erratum: MirGeneDB 2.0: The metazoan microRNA complement (Nucleic Acids Research (2019) DOI: 10.1093/nar/gkz885). Nucleic Acids Research (NAR). ISSN 0305-1048. 48(1). doi: 10.1093/nar/gkz1016.
• Stansberg, Christine; Willassen, Nils P; Thomassen, Gard O Sundby; Hovig, Johannes Eivind & Jonassen, Inge (2020). How open databases turn out to be crucial in the fight against Covid-19. NBS-nytt. ISSN 0801-3535. 4, p. 38–43.
• Bösl, Korbinian; Ghavidel, Fatemeh; Tekle, Kidane M; Kleppe, Rune; Hjerde, Erik & Drabløs, Finn [Show all 11 contributors for this article] (2020). End-to-End Data Management Toolkit for Norwegian Life Scientists. Show summary

  Major funding agencies require the successful planning and implementation of Data Management. In addition to obtaining funding, good Data Management also makes research more efficient, facilitates collaboration and saves time and resources. ELIXIR Norway and the Centre for Digital Life Norway have established an End-to-End toolkit, covering the whole data life cycle from proposal to publication, providing practical, existing solutions, available to Norwegian Life Scientists to make their research FAIR (Findable, Accessible, Interoperable and Reusable). We provide access to the Data Steward Wizard tool as one solution to identify data management needs, plan Data Management budgets and to produce a Data Management Plans (DMPs) according to the specifications by filling an interactive, well-documented questionnaire. NeLS - the Norwegian e-Infrastructure for Life Sciences is a versatile and backuped storage solution for Life Science data. NeLS is directly integrated with Galaxy, an open, web-based platform for accessible, reproducible, and transparent computational biological research, without the need of programming skills. We have further developed a integration of NeLS with FAIRDOMHub/SEEK, a resource platform for managing data-sets and models in projects and sharing at publication. ELIXIR maintains as variety of data deposition databases that are suited to host sensitive and non-sensitive data. Usage of this deposition repositories also maximises the visibility of published research.

• Rye, Morten Beck; Nygård, Ståle; Drabløs, Finn; Petersen, Kjell; Våge, Dag Inge & Willassen, Nils Peder [Show all 8 contributors for this article] (2019). ELIXIR.NO - The national infrastructure of bioinformatics.
• Bai, Baoyan; Vodák, Daniel; Nakken, Sigve; Wise, Jillian; Blaker, Yngvild Nuvin & Lingjærde, Ole Christian [Show all 18 contributors for this article] (2019). Deep profiling of genetic aberrations and clonal evolution in follicular lymphoma. Blood. ISSN 0006-4971. 134(1), p. 20–20. doi: 10.1182/blood-2019-128403.
• Møller, Pål & Hovig, Eivind (2018). Retraction Note to: The BRCA2 variant c.68–7 T > A is associated with breast cancer. Hereditary Cancer in Clinical Practice. ISSN 1731-2302. 16(1). doi: 10.1186/s13053-018-0093-1.
• Nakken, Sigve; Fournous, Ghislain; Vodak, Daniel; Aasheim, Lars Birger; Myklebost, Ola & Hovig, Eivind (2018). Personal Cancer Genome Reporter: Variant interpretation report for precision oncology. Bioinformatics. ISSN 1367-4803. 34(10), p. 1778–1780. doi: 10.1093/bioinformatics/btx817. Full text in Research Archive
• Drabløs, Finn; Nygård, Ståle; Petersen, Kjell; Våge, Dag Inge; Willassen, Nils Peder & Hovig, Eivind [Show all 7 contributors for this article] (2017). ELIXIR.NO - The national infrastructure for bioinformatics.
• Kanduri, Chakravarthi; Domanska, Diana; Hovig, Eivind & Sandve, Geir Kjetil (2017). Genome build information is an essential part of genomic track files. Genome Biology. ISSN 1465-6906. 18(1). doi: 10.1186/s13059-017-1312-1.
• Misund, Kristine; Hofste op Bruinink, Davine; Coward, Eivind; Hoogenboezem, Remco; Rustad, Even Holth & Hovig, Eivind [Show all 10 contributors for this article] (2017). Detection of mutations in Multiple Myeloma during different stages of disease.
• Møller, Pål & Hovig, Eivind (2017). Our genes, our selves: hereditary breast cancer and biological citizenship in Norway. Medicine, Health care and Philosophy. ISSN 1386-7423. Published ahead of print, p. 1–4. doi: 10.1007/s11019-017-9803-0.
• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: MoBaPsychGen pipeline v.1. Cold Spring Harbor Laboratory Press (CSHL). ISSN 2692-8205. (2022). Show summary

  Background: The Norwegian Mother, Father, and Child Cohort Study (MoBa) is a population-based pregnancy cohort, which includes approximately 114,500 children, 95,200 mothers, and 75,200 fathers. Genotyping of MoBa has been conducted through multiple research projects, spanning several years; using varying selection criteria, genotyping arrays, and genotyping centres. MoBa contains numerous interrelated families, which necessitated the implementation of a family-based quality control (QC) pipeline that verifies and accounts for diverse types of relatedness. Methods: The MoBaPsychGen pipeline, comprising pre-imputation QC, phasing, imputation, and post-imputation QC, was developed based on current best-practice protocols and implemented to account for the complex structure of the MoBa genotype data. The pipeline includes QC on both single nucleotide polymorphism (SNP) and individual level. Phasing and imputation were performed using the publicly available Haplotype Reference Consortium release 1.1 panel as a reference. Information from the Medical Birth Registry of Norway and MoBa questionnaires were used to identify biological sex, year of birth, reported parent-offspring (PO) relationships, and multiple births (only available in the offspring generation). Results: In total, 207,569 unique individuals (90% of the unique individuals included in the study) and 6,981,748 SNPs passed the MoBaPsychGen pipeline. The relatedness checks performed throughout the pipeline allowed identification of within-generation and across-generation first-degree, second-degree, and third-degree relatives. The individuals passing post-imputation QC comprised 64,471 families ranging in size from singletons to 84 unique individuals (singletons are included as families as other family members may not have been genotyped, imputed, or passed post-imputation QC). The relationships identified include 287 monozygotic twin pairs, 22,884 full siblings, 117,004 PO pairs, 23,299 second-degree relative pairs, and 10,828 third-degree relative pairs. Discussion: MoBa contains a highly complex relatedness structure, with a variety of family structures including singletons, PO duos, full (mother, father, child) PO trios, nuclear families, blended families, and extended families. The availability of robustly quality-controlled genetic data for such a large cohort with a unique extended family structure will allow many novel research questions to be addressed. Furthermore, the MoBaPsychGen pipeline has potential utility in similar cohorts.

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