Improved clinical decisions via integrating multiple data levels to overcome chemotherapy resistance in high-grade serous ovarian cancer

Livrables

Project Office and Knowledge Management System up and running

Project Office and Knowledge Management System up and running Operational Project manager allocated for the project and external and internal websites done Members of Exploitation and Dissemination panels assigned Materials for project presentation produced

Completion of UH retrospective HGSOC cohort

Completion of UH retrospective HGSOC cohort.

First study subject approvals package

First study subject approvals package Final version of observational study protocol approved by the local Ethics committee and the study protocol of the first observational part will be submitted to ClinicalTrialscov for registration

Midterm recruitment report

Midterm recruitment report. At the time point when 50% of the study population is expected to have been recruited.

Bayesian network method ready for dynamic multi-omics integration

Bayesian network method ready for dynamic multi-omics integration.

Set up of single-cell RNA-seq and cell hashing for HGSOC

Set up of singlecell RNAseq and cell hashing for HGSOC

First study subject approvals package: Final version of clinical trial protocol

First study subject approvals package. Final version of clinical trial protocol: Study protocol approved by local Ethics committee, TUCH and FIMEA. Clinical trial protocol submitted to ClinicalTrials.cov for registration.

Preliminary report on regulatory issues in personalised medicine

Preliminary report on regulatory issues in personalised medicine.

Full design documentation for the eXplAIner software

Data Management Plan

Data Management Plan A detailed and updated Data Management Plan available on the project website where the latest updated version will be available

Fully functional, documented, and publicly available open-source eXplAIner software

Fully functional, documented, and publicly available open-source eXplAIner software.

Publications

TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening

Auteurs: Miguel M. Álvarez, Josep Biayna & Fran Supek
Publié dans: Nature Communications, Numéro 13(4520), 2022, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-022-32285-1

Activation of invasion by oncogenic reprogramming of cholesterol metabolism via increased NPC1 expression and macropinocytosis

Auteurs: Aikaterini Skorda, Anna Røssberg Lauridsen, Chengnan Wu, Jinrong Huang, Monika Mrackova, Nuggi Ingholt Winther, Vanessa Jank , Zsofia Sztupinszki, Robert Strauss , Mesut Bilgin, Kenji Maeda, Bin Liu, Yonglun Luo, Marja Jäättelä,Tuula Kallunki
Publié dans: Oncogene, 2023, ISSN 1476-5594
Éditeur: Springer Nature Publishing Company
DOI: 10.1038/s41388-023-02771-x

Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level

Auteurs: Anna Perkiö, Barun Pradhan, Fatih Genc, Anna Pirttikoski, Sanna Pikkusaari, Erdogan Pekcan Erkan, Matias Marin Falco, Kaisa Huhtinen, Sara Narva, Johanna Hynninen, Liisa Kauppi, Anna Vähärautio
Publié dans: Scientific Reports, Numéro 14, 2024, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-024-54113-w

POIBM: batch correction of heterogeneous RNA-seq datasets through latent sample matching

Auteurs: Susanna Holmström, Sampsa Hautaniemi, Antti Häkkinen
Publié dans: Bioinformatics, 2022, ISSN 1460-2059
Éditeur: Oxford University Press
DOI: 10.1093/bioinformatics/btac124

An overview of machine learning methods for monotherapy drug response prediction.

Auteurs: Farzaneh Firoozbakht, Behnam Yousefi, Benno Schwikowski
Publié dans: Briefings in Bioinformatics, Numéro 23:1, 2022, ISSN 1477-4054
Éditeur: Oxford, United Kingdom
DOI: 10.1093/bib/bbab408

Cell cycle alterations associate with a redistribution of mutation rates across chromosomal domains in human cancers

Auteurs: Marina Salvadores, Fran Supek
Publié dans: Nature Cancer, 2024, ISSN 2662-1347
Éditeur: Nature Research
DOI: 10.1038/s43018-023-00707-8

Integrating knowledge and omics to decipher mechanisms via large-scale models of signaling networks

Auteurs: Martin Garrido-Rodriguez , Katharina Zirngibl, Olga Ivanova, Sebastian Lobentanzer, Julio Saez-Rodriguez
Publié dans: Molecular Systems Biology, Numéro 18, 2022, ISSN 1744-4292
Éditeur: Nature Publishing Group
DOI: 10.15252/msb.202211036

Bexmarilimab Activates Human Tumor-Associated Macrophages to Support Adaptive Immune Responses in Interferon-Poor Immune Microenvironments

Auteurs: Jenna H. Rannikko, Petri Bono, Johanna Hynninen, Maija Hollmén
Publié dans: Cancer Immunol Res, Numéro 12(1), 2024, Page(s) 48-59, ISSN 2326-6074
Éditeur: American Association for Cancer Research
DOI: 10.1158/2326-6066.cir-23-0350

QuantISH: RNA in situ hybridization image analysis framework for quantifying cell type-specific target RNA expression and variability

Auteurs: Sanaz Jamalzadeh, Antti Häkkinen, Noora Andersson, Kaisa Huhtinen, Anna Laury, Sakari Hietanen, Johanna Hynninen,Jaana Oikkonen, Olli Carpén, Anni Virtanen, Sampsa Hautaniemi
Publié dans: Laboratory Investigation, 2022, ISSN 1530-0307
Éditeur: Nature Publishing Group
DOI: 10.1038/s41374-022-00743-5

The impact of rare germline variants on human somatic mutation processes

Auteurs: Mischan Vali-Pour, Ben Lehner, Fran Supek
Publié dans: Nature Communications, Numéro 13, 2022, Page(s) 3724, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-022-31483-1

Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma

Auteurs: Mai T.N. Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Publié dans: Biomedicine & Pharmacotherapy, Numéro 168, 2023, ISSN 1950-6007
Éditeur: Elsevier B.V
DOI: 10.1016/j.biopha.2023.115630

A survey on data integration for multi-omics sample clustering

Auteurs: Marta Lovino; Vincenzo Randazzo; Gabriele Ciravegna; Pietro Barbiero; Elisa Ficarra; Giansalvo Cirrincione
Publié dans: Neurocomputing, Numéro 488, 2022, Page(s) 494-508, ISSN 0925-2312
Éditeur: Elsevier BV
DOI: 10.1016/j.neucom.2021.11.094

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer

Auteurs: Molly J. Carroll, Katja Kaipio, Johanna Hynninen, Olli Carpen, Sampsa Hautaniemi, David Page, Pamela K. Kreeger
Publié dans: Cancers, Numéro 14(17), 2022, ISSN 2072-6694
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers14174291

Proton and alpha radiation-induced mutational profiles in human cells

Auteurs: Tiffany M. Delhomme, Maia Munteanu, Manuela Buonanno, Veljko Grilj, Josep Biayna & Fran Supek
Publié dans: Scientific Reports, Numéro 13(9791), 2023, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-023-36845-3

A Graph-Based Multi-Scale Approach with Knowledge Distillation for WSI Classification

Auteurs: Gianpaolo Bontempo; Federico Bolelli; Angelo Porrello; Simone Calderara; Elisa Ficarra
Publié dans: IEEE Transaction on medical imging, 2023, ISSN 0278-0062
Éditeur: Institute of Electrical and Electronics Engineers
DOI: 10.1109/tmi.2023.3337549

Genome-wide quantification of copy-number aberration impact on gene expression in ovarian high-grade serous carcinoma

Auteurs: Sanaz Jamalzadeh, Jun Dai, Kari Lavikka, Yilin Li, Jing Jiang, Kaisa Huhtinen, Anni Virtanen, Jaana Oikkonen, Sakari Hietanen, Johanna Hynninen, Anna Vähärautio, Antti Häkkinen* and Sampsa Hautaniemi*
Publié dans: BMC Cancer, Numéro 24:173, 2024, ISSN 1471-2407
Éditeur: BioMed Central
DOI: 10.1186/s12885-024-11895-6

Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy

Auteurs: David Mas-Ponte, Marcel McCullough, Fran Supek
Publié dans: Clinical Science, Numéro 136 (5), 2022, Page(s) 383–404, ISSN 1470-8736
Éditeur: Portland Press Limited
DOI: 10.1042/cs20210682

Quantification of cell death and proliferation of patient-derived ovarian cancer organoids through 3D imaging and image analysis

Auteurs: Aikaterini Skorda, Anna Røssberg Lauridsen, Kaisa Huhtinen, Alexandra Lahtinen, Wojciech Senkowski, Jaana Oikkonen, Johanna Hynninen, Sampsa Hautaniemi. Tuula Kallunki
Publié dans: STAR Protocols, Numéro 4(4), 2023, ISSN 2666-1667
Éditeur: Elsevier B.V
DOI: 10.1016/j.xpro.2023.102683

Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer.

Auteurs: Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
Publié dans: Basic & Clinical Pharmacology & Toxicology, Numéro 1-11, 2023, ISSN 1742-7843
Éditeur: John Wiley & Sons, Inc.
DOI: 10.1111/bcpt.13866

Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention.

Auteurs: Juuli Raivola, Alice Dini, Hanna Karvonen, Emilia Piki, Kari Salokas, Wilhelmiina Niininen, Laura Kaleva, Kaiyang Zhang, Mariliina Arjama, Greta Gudoityte, Brinton Seashore-Ludlow, Markku Varjosalo, Olli Kallioniemi, Sampsa Hautaniemi, Astrid Murumägi & Daniela Ungureanu
Publié dans: Cell Death and Disease, Numéro 13, 2022, ISSN 2041-4889
Éditeur: Nature Publishing Group
DOI: 10.1038/s41419-022-05161-5

Prevalence, causes and impact of TP53-loss phenocopying events in human tumors

Auteurs: Bruno Fito-Lopez; Marina Salvadores; Miguel-Martin Alvarez; Fran Supek
Publié dans: BMC Biology, Numéro 21(92), 2023, ISSN 1741-7007
Éditeur: BioMed Central
DOI: 10.1186/s12915-023-01595-1

H&E image analysis pipeline for quantifying morphological features

Auteurs: Valeria Ariotta, Oskari Lehtonen, Shams Salloum, Giulia Micoli, Kari Lavikka, Ville Rantanen, Johanna Hynninen, Anni Virtanen, Sampsa Hautaniemi
Publié dans: Journal of Pathology Informatics, Numéro 14, 2023, ISSN 2153-3539
Éditeur: Elsevier B.V
DOI: 10.1016/j.jpi.2023.100339

MiREx: mRNA levels prediction from gene sequence and miRNA target knowledge

Auteurs: Elena Pianfetti; Marta Lovino; Elisa Ficarra; Loredana Martignetti
Publié dans: BMC Bioinformatics, Numéro 24, 2023, ISSN 1471-2105
Éditeur: BioMed Central
DOI: 10.1186/s12859-023-05560-1

Exploiting generative self-supervised learning for the assessment of biological images with lack of annotations

Auteurs: Alessio Mascolini; Dario Cardamone; Francesco Ponzio; Santa Di Cataldo; Elisa Ficarra
Publié dans: BMC Bioinformatics, Numéro 23(295), 2022, ISSN 1471-2105
Éditeur: BioMed Central
DOI: 10.1186/s12859-022-04845-1

Predicting gene and protein expression levels from DNA and protein sequences with Perceiver

Auteurs: Matteo Stefanini; Marta Lovino; Rita Cucchiara; Elisa Ficarra
Publié dans: Computer Methods and Programs in Biomedicine, Numéro 234, 2023, ISSN 1872-7565
Éditeur: Elsevier B.V
DOI: 10.1101/2022.09.21.508821

Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes

Auteurs: Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Jaana Oikkonen, Yilin Li, Fernando Perez-Villatoro, Taru Muranen, Matilda Salko, Kaisa Huhtinen, Anna Kanerva, Heidi Koskela, Johanna Tapper, Riitta Koivisto-Korander, Titta Joutsiniemi, Ulla-Maija Haltia, Heini Lassus, Sampsa Hautaniemi, Anniina Färkkilä, Johanna Hynninen, Sakari Hietanen, Olli Carpen, Liisa Kauppi
Publié dans: Clinical Cancer Research, Numéro 1557-3265, 2023, Page(s) OF1–OF14, ISSN 1557-3265
Éditeur: American Association for Cancer Research
DOI: 10.1158/1078-0432.ccr-22-3156

ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity

Auteurs: Emilia Piki, Alice Dini, Juuli Raivola, Kari Salokas, Kaiyang Zhang, Markku Varjosalo, Teijo Pellinen, Katja Välimäki, Kristina Tabor Veskimäe, Synnöve Staff, Sampsa Hautaniemi, Astrid Murumägi, Daniela Ungureanu
Publié dans: Cell Death Discovery, Numéro 9 (222), 2023, ISSN 2058-7716
Éditeur: Nature Publishing Group
DOI: 10.1038/s41420-023-01527-6

Auteurs: Heidi Koskela, Yilin Li, Titta Joutsiniemi, Taru Muranen, Veli-Matti Isoviita, Kaisa Huhtinen, Giulia Micoli, Kari Lavikka, Giovanni Marchi, Sakari Hietanen, Anni Virtanen, Sampsa Hautaniemi, Jaana Oikkonen, Johanna Hynninen
Publié dans: Gynecologic Oncology, Numéro 180, 2024, Page(s) 91-98, ISSN 1095-6859
Éditeur: Elsevier B.V
DOI: 10.1016/j.ygyno.2023.11.027

Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma

Auteurs: Alexandra Lahtinen; Kari Lavikka; Anni Virtanen; Yilin Li; Sanaz Jamalzadeh; Aikaterini Skorda; Anna Røssberg Lauridsen; Kaiyang Zhang; Giovanni Marchi; Veli-Matti Isoviita; Valeria Ariotta; Oskari Lehtonen; Taru A. Muranen; Kaisa Huhtinen; Olli Carpén; Sakari Hietanen; Wojciech Senkowski; Tuula Kallunki; Antti Häkkinen; Johanna Hynninen; Jaana Oikkonen; Sampsa Hautaniemi
Publié dans: Cancer Cell, Numéro 41, 2023, Page(s) 1103–1117, ISSN 1878-3686
Éditeur: Elsevier B.V
DOI: 10.1016/j.ccell.2023.04.017

Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises

Auteurs: Aikaterini Skorda, Marie Lund Bay, Sampsa Hautaniemi, Alexandra Lahtinen, Tuula Kallunki
Publié dans: Cancers, Numéro 14(24), 2022, ISSN 2072-6694
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers14246257

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

Auteurs: Kaiyang Zhang, Erdogan Pekcan Erkan, Sanaz Jamalzadeh, Jun Dai, Noora Andersson, Katja Kaipio, Tarja Lamminen, Naziha Mansuri, Kaisa Huhtinen, Olli Carpén, Sakari Hietanen, Jaana Oikkonen, Johanna Hynninen, Anni Virtanen, Antti Häkkinen, Sampsa Hautaniemi, Anna Vähärautio
Publié dans: Science Advances, Numéro eabm1831, 2022, ISSN 2375-2548
Éditeur: American Association for the Advancement of Science
DOI: 10.1126/sciadv.abm1831

Identifying the oncogenic potential of gene fusions exploiting miRNAs

Auteurs: Marta Lovino, Marilisa Montemurro, Venere S Barrese, Elisa Ficarra
Publié dans: Journal of Biomedical Informatics, Numéro 129, 2022, ISSN 1532-0464
Éditeur: Academic Press
DOI: 10.1016/j.jbi.2022.104057

Artificial intelligence-based image analysis can predict outcome in high-grade serous carcinoma via histology alone

Auteurs: Anna Ray Laury, Sami Blom, Tuomas Ropponen, Anni Virtanen, Olli Mikael Carpén
Publié dans: Scientific Reports, Numéro 11/1, 2021, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-021-98480-0

Mutational signatures are markers of drug sensitivity of cancer cells

Auteurs: Levatić, Jurica; Salvadores, Marina; Fuster-Tormo, Francisco; Supek, Fran; Universitat Autònoma de Barcelona
Publié dans: Nature Communications, Numéro 13, 2022, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1101/2021.05.19.444811

PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures

Auteurs: Heidi Rausio, Alejandra Cervera, Vanina D. Heuser, Gun West, Jaana Oikkonen, Elena Pianfetti, Marta Lovino, Elisa Ficarra, Pekka Taimen, Johanna Hynninen, Rainer Lehtonen, Sampsa Hautaniemi, Olli Carpén, Kaisa Huhtinen
Publié dans: Neoplasia, Numéro 51, 2024, ISSN 1476-5586
Éditeur: Elsevier B.V
DOI: 10.1016/j.neo.2024.100987

Democratizing knowledge representation with BioCypher

Auteurs: Sebastian Lobentanzer, Patrick Aloy, Jan Baumbach, Balazs Bohar, Vincent J. Carey, Pornpimol Charoentong, Katharina Danhauser, Tunca Doğan, Johann Dreo, Ian Dunham, Elias Farr, Adrià Fernandez-Torras, Benjamin M. Gyori, Michael Hartung, Charles Tapley Hoyt, Christoph Klein, Tamas Korcsmaros, Andreas Maier, Matthias Mann, David Ochoa, Elena Pareja-Lorente, Ferdinand Popp, Martin Preusse, Niklas P
Publié dans: Nature Biotechnology, Numéro 41, 2023, Page(s) 1056–1059, ISSN 1546-1696
Éditeur: Nature Publishing Group
DOI: 10.1038/s41587-023-01848-y

Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer.

Auteurs: "Fernando Perez-Villatoro, Jaana Oikkonen, Julia Casado, Anastasiya Chernenko, Doga C. Gulhan, Manuela Tumiati, Yilin Li, Kari Lavikka, Sakari Hietanen, Johanna Hynninen, Ulla-Maija Haltia, Jaakko S. Tyrmi, Hannele Laivuori, Panagiotis A. Konstantinopoulos, Sampsa Hautaniemi, Liisa Kauppi, Anniina Färkkilä """
Publié dans: NPJ Precision Oncology, Numéro 6(1), 2022, Page(s) 96, ISSN 2397-768X
Éditeur: Nature Publishing Group
DOI: 10.1038/s41698-022-00339-8

Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence

Auteurs: Giovanni Marchi, Anna Rajavuori, Mai T N Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Publié dans: Translational Oncology, Numéro 2(39), 2023, ISSN 1944-7124
Éditeur: Elsevier B.V
DOI: 10.1016/j.tranon.2023.101814

Paving the Path for Sustainable and Responsible Off-Label Use of Pharmaceutical Products in Europe

Auteurs: Miquel Díaz Hernández; Waltter Roslin; Juli Mansnérus
Publié dans: European Journal of Health Law, Numéro 31(2), 2024, Page(s) 129–152, ISSN 1571-8093
Éditeur: Brill
DOI: 10.1163/15718093-bja10123

Predicting gene expression levels from DNA sequences and post-transcriptional information with transformers

Auteurs: Vittorio Pipoli; Mattia Cappelli; Alessandro Palladini; Carlo Peluso; Marta Lovino; Elisa Ficarra
Publié dans: Computer Methods and Programs in Biomedicine, Numéro 225, 2022, ISSN 1872-7565
Éditeur: Elsevier B.V
DOI: 10.1016/j.cmpb.2022.107035

From the integrity of potency assays to safe clinical intervention: Legal perspectives.

Auteurs: Waltter Roslin, Juli Mansnérus
Publié dans: Potency Assays for Advanced Stem Cell Therapy Medicinal Products, Numéro 1, 2023, Page(s) 151-163, ISBN 978-3-031-30039-4
Éditeur: Springer Publishing Company
DOI: 10.1007/978-3-031-30040-0_10

Lääkkeiden off label -käyttö lapsipotilailla: lapsen osallisuuden oikeudelliset reunaehdot

Auteurs: Juli Mansnérus, Charlotta Bonsdorff, Petro Vornanen
Publié dans: Terveys ja lapsen oikeudet, Numéro 2023:7, 2023, Page(s) 190-203, ISBN 978-952-400-747-4
Éditeur: Office of the Ombudsman for Children

FusionFlow: An Integrated System Workflow for Gene Fusion Detection in Genomic Samples

Auteurs: Federica Citarrella; Gianpaolo Bontempo; Marta Lovino; Elisa Ficarra
Publié dans: New Trends in Database and Information Systems, 2022, ISBN 978-3-031-15743-1
Éditeur: Springer Publishing Company
DOI: 10.1007/978-3-031-15743-1_8

Enhancing PFI Prediction with GDS-MIL: A Graph-based Dual Stream MIL Approach

Auteurs: Gianpaolo Bontempo, Nicola Bartolini, Marta Lovino, Federico Bolelli, Anni Virtanen, Elisa Ficarra
Publié dans: Lecture Notes in Computer Science, Numéro 14233, 2023, Page(s) 550-562, ISSN 1611-3349
Éditeur: Springer
DOI: 10.1007/978-3-031-43148-7_46

DAS-MIL: Distilling Across Scales for MIL Classification of Histological WSIs

Auteurs: Bontempo, Gianpaolo; Porrello, Angelo; Bolelli, Federico; Calderara, Simone; Ficarra, Elisa
Publié dans: Lecture Notes in Computer Science, Numéro 14220, 2023, Page(s) 248-258, ISSN 1611-3349
Éditeur: Springer
DOI: 10.1007/978-3-031-43907-0_24

Buffer-MIL: Robust Multi-instance Learning with a Buffer-based Approach

Auteurs: Gianpaolo Bontempo, Luca Lumetti, Angelo Porrello, Federico Bolelli, Simone Calderara, Elisa Ficarra
Publié dans: Lecture Notes in Computer Science, Numéro 14234, 2023, Page(s) 1-12, ISSN 1611-3349
Éditeur: Springer
DOI: 10.1007/978-3-031-43153-1_1

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