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

Risultati finali

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.

Pubblicazioni

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

Autori: Miguel M. Álvarez, Josep Biayna & Fran Supek
Pubblicato in: Nature Communications, Numero 13(4520), 2022, ISSN 2041-1723
Editore: 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

Autori: 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
Pubblicato in: Oncogene, 2023, ISSN 1476-5594
Editore: 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

Autori: 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
Pubblicato in: Scientific Reports, Numero 14, 2024, ISSN 2045-2322
Editore: Nature Publishing Group
DOI: 10.1038/s41598-024-54113-w

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

Autori: Susanna Holmström, Sampsa Hautaniemi, Antti Häkkinen
Pubblicato in: Bioinformatics, 2022, ISSN 1460-2059
Editore: Oxford University Press
DOI: 10.1093/bioinformatics/btac124

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

Autori: Farzaneh Firoozbakht, Behnam Yousefi, Benno Schwikowski
Pubblicato in: Briefings in Bioinformatics, Numero 23:1, 2022, ISSN 1477-4054
Editore: Oxford, United Kingdom
DOI: 10.1093/bib/bbab408

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

Autori: Marina Salvadores, Fran Supek
Pubblicato in: Nature Cancer, 2024, ISSN 2662-1347
Editore: Nature Research
DOI: 10.1038/s43018-023-00707-8

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

Autori: Martin Garrido-Rodriguez , Katharina Zirngibl, Olga Ivanova, Sebastian Lobentanzer, Julio Saez-Rodriguez
Pubblicato in: Molecular Systems Biology, Numero 18, 2022, ISSN 1744-4292
Editore: Nature Publishing Group
DOI: 10.15252/msb.202211036

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

Autori: Jenna H. Rannikko, Petri Bono, Johanna Hynninen, Maija Hollmén
Pubblicato in: Cancer Immunol Res, Numero 12(1), 2024, Pagina/e 48-59, ISSN 2326-6074
Editore: 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

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

The impact of rare germline variants on human somatic mutation processes

Autori: Mischan Vali-Pour, Ben Lehner, Fran Supek
Pubblicato in: Nature Communications, Numero 13, 2022, Pagina/e 3724, ISSN 2041-1723
Editore: 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

Autori: Mai T.N. Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Pubblicato in: Biomedicine & Pharmacotherapy, Numero 168, 2023, ISSN 1950-6007
Editore: Elsevier B.V
DOI: 10.1016/j.biopha.2023.115630

A survey on data integration for multi-omics sample clustering

Autori: Marta Lovino; Vincenzo Randazzo; Gabriele Ciravegna; Pietro Barbiero; Elisa Ficarra; Giansalvo Cirrincione
Pubblicato in: Neurocomputing, Numero 488, 2022, Pagina/e 494-508, ISSN 0925-2312
Editore: 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

Autori: Molly J. Carroll, Katja Kaipio, Johanna Hynninen, Olli Carpen, Sampsa Hautaniemi, David Page, Pamela K. Kreeger
Pubblicato in: Cancers, Numero 14(17), 2022, ISSN 2072-6694
Editore: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers14174291

Proton and alpha radiation-induced mutational profiles in human cells

Autori: Tiffany M. Delhomme, Maia Munteanu, Manuela Buonanno, Veljko Grilj, Josep Biayna & Fran Supek
Pubblicato in: Scientific Reports, Numero 13(9791), 2023, ISSN 2045-2322
Editore: Nature Publishing Group
DOI: 10.1038/s41598-023-36845-3

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

Autori: Gianpaolo Bontempo; Federico Bolelli; Angelo Porrello; Simone Calderara; Elisa Ficarra
Pubblicato in: IEEE Transaction on medical imging, 2023, ISSN 0278-0062
Editore: 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

Autori: 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*
Pubblicato in: BMC Cancer, Numero 24:173, 2024, ISSN 1471-2407
Editore: 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

Autori: David Mas-Ponte, Marcel McCullough, Fran Supek
Pubblicato in: Clinical Science, Numero 136 (5), 2022, Pagina/e 383–404, ISSN 1470-8736
Editore: 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

Autori: Aikaterini Skorda, Anna Røssberg Lauridsen, Kaisa Huhtinen, Alexandra Lahtinen, Wojciech Senkowski, Jaana Oikkonen, Johanna Hynninen, Sampsa Hautaniemi. Tuula Kallunki
Pubblicato in: STAR Protocols, Numero 4(4), 2023, ISSN 2666-1667
Editore: 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.

Autori: Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
Pubblicato in: Basic & Clinical Pharmacology & Toxicology, Numero 1-11, 2023, ISSN 1742-7843
Editore: 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.

Autori: 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
Pubblicato in: Cell Death and Disease, Numero 13, 2022, ISSN 2041-4889
Editore: Nature Publishing Group
DOI: 10.1038/s41419-022-05161-5

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

Autori: Bruno Fito-Lopez; Marina Salvadores; Miguel-Martin Alvarez; Fran Supek
Pubblicato in: BMC Biology, Numero 21(92), 2023, ISSN 1741-7007
Editore: BioMed Central
DOI: 10.1186/s12915-023-01595-1

H&E image analysis pipeline for quantifying morphological features

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

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

Autori: Elena Pianfetti; Marta Lovino; Elisa Ficarra; Loredana Martignetti
Pubblicato in: BMC Bioinformatics, Numero 24, 2023, ISSN 1471-2105
Editore: BioMed Central
DOI: 10.1186/s12859-023-05560-1

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

Autori: Alessio Mascolini; Dario Cardamone; Francesco Ponzio; Santa Di Cataldo; Elisa Ficarra
Pubblicato in: BMC Bioinformatics, Numero 23(295), 2022, ISSN 1471-2105
Editore: BioMed Central
DOI: 10.1186/s12859-022-04845-1

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

Autori: Matteo Stefanini; Marta Lovino; Rita Cucchiara; Elisa Ficarra
Pubblicato in: Computer Methods and Programs in Biomedicine, Numero 234, 2023, ISSN 1872-7565
Editore: 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

Autori: 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
Pubblicato in: Clinical Cancer Research, Numero 1557-3265, 2023, Pagina/e OF1–OF14, ISSN 1557-3265
Editore: American Association for Cancer Research
DOI: 10.1158/1078-0432.ccr-22-3156

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

Autori: 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
Pubblicato in: Cell Death Discovery, Numero 9 (222), 2023, ISSN 2058-7716
Editore: Nature Publishing Group
DOI: 10.1038/s41420-023-01527-6

Autori: 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
Pubblicato in: Gynecologic Oncology, Numero 180, 2024, Pagina/e 91-98, ISSN 1095-6859
Editore: 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

Autori: 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
Pubblicato in: Cancer Cell, Numero 41, 2023, Pagina/e 1103–1117, ISSN 1878-3686
Editore: Elsevier B.V
DOI: 10.1016/j.ccell.2023.04.017

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

Autori: Aikaterini Skorda, Marie Lund Bay, Sampsa Hautaniemi, Alexandra Lahtinen, Tuula Kallunki
Pubblicato in: Cancers, Numero 14(24), 2022, ISSN 2072-6694
Editore: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers14246257

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

Autori: 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
Pubblicato in: Science Advances, Numero eabm1831, 2022, ISSN 2375-2548
Editore: American Association for the Advancement of Science
DOI: 10.1126/sciadv.abm1831

Identifying the oncogenic potential of gene fusions exploiting miRNAs

Autori: Marta Lovino, Marilisa Montemurro, Venere S Barrese, Elisa Ficarra
Pubblicato in: Journal of Biomedical Informatics, Numero 129, 2022, ISSN 1532-0464
Editore: 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

Autori: Anna Ray Laury, Sami Blom, Tuomas Ropponen, Anni Virtanen, Olli Mikael Carpén
Pubblicato in: Scientific Reports, Numero 11/1, 2021, ISSN 2045-2322
Editore: Nature Publishing Group
DOI: 10.1038/s41598-021-98480-0

Mutational signatures are markers of drug sensitivity of cancer cells

Autori: Levatić, Jurica; Salvadores, Marina; Fuster-Tormo, Francisco; Supek, Fran; Universitat Autònoma de Barcelona
Pubblicato in: Nature Communications, Numero 13, 2022, ISSN 2041-1723
Editore: 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

Autori: 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
Pubblicato in: Neoplasia, Numero 51, 2024, ISSN 1476-5586
Editore: Elsevier B.V
DOI: 10.1016/j.neo.2024.100987

Democratizing knowledge representation with BioCypher

Autori: 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
Pubblicato in: Nature Biotechnology, Numero 41, 2023, Pagina/e 1056–1059, ISSN 1546-1696
Editore: Nature Publishing Group
DOI: 10.1038/s41587-023-01848-y

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

Autori: "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 """
Pubblicato in: NPJ Precision Oncology, Numero 6(1), 2022, Pagina/e 96, ISSN 2397-768X
Editore: 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

Autori: Giovanni Marchi, Anna Rajavuori, Mai T N Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Pubblicato in: Translational Oncology, Numero 2(39), 2023, ISSN 1944-7124
Editore: 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

Autori: Miquel Díaz Hernández; Waltter Roslin; Juli Mansnérus
Pubblicato in: European Journal of Health Law, Numero 31(2), 2024, Pagina/e 129–152, ISSN 1571-8093
Editore: Brill
DOI: 10.1163/15718093-bja10123

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

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

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

Autori: Waltter Roslin, Juli Mansnérus
Pubblicato in: Potency Assays for Advanced Stem Cell Therapy Medicinal Products, Numero 1, 2023, Pagina/e 151-163, ISBN 978-3-031-30039-4
Editore: Springer Publishing Company
DOI: 10.1007/978-3-031-30040-0_10

Lääkkeiden off label -käyttö lapsipotilailla: lapsen osallisuuden oikeudelliset reunaehdot

Autori: Juli Mansnérus, Charlotta Bonsdorff, Petro Vornanen
Pubblicato in: Terveys ja lapsen oikeudet, Numero 2023:7, 2023, Pagina/e 190-203, ISBN 978-952-400-747-4
Editore: Office of the Ombudsman for Children

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

Autori: Federica Citarrella; Gianpaolo Bontempo; Marta Lovino; Elisa Ficarra
Pubblicato in: New Trends in Database and Information Systems, 2022, ISBN 978-3-031-15743-1
Editore: 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

Autori: Gianpaolo Bontempo, Nicola Bartolini, Marta Lovino, Federico Bolelli, Anni Virtanen, Elisa Ficarra
Pubblicato in: Lecture Notes in Computer Science, Numero 14233, 2023, Pagina/e 550-562, ISSN 1611-3349
Editore: Springer
DOI: 10.1007/978-3-031-43148-7_46

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

Autori: Bontempo, Gianpaolo; Porrello, Angelo; Bolelli, Federico; Calderara, Simone; Ficarra, Elisa
Pubblicato in: Lecture Notes in Computer Science, Numero 14220, 2023, Pagina/e 248-258, ISSN 1611-3349
Editore: Springer
DOI: 10.1007/978-3-031-43907-0_24

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

Autori: Gianpaolo Bontempo, Luca Lumetti, Angelo Porrello, Federico Bolelli, Simone Calderara, Elisa Ficarra
Pubblicato in: Lecture Notes in Computer Science, Numero 14234, 2023, Pagina/e 1-12, ISSN 1611-3349
Editore: Springer
DOI: 10.1007/978-3-031-43153-1_1

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