Kari Lavikka

University of Helsinki | HY · Research Programs Unit

Background Visualization is an indispensable facet of genomic data analysis. Despite the abundance of specialized visualization tools, there remains a distinct need for tailored solutions. However, their implementation typically requires extensive programming expertise from bioinformaticians and software developers, especially when building interac...

Copy-number alterations (CNAs) are a hallmark of cancer and can regulate cancer cell states via altered gene expression values. Herein, we have developed a copy-number impact (CNI) analysis method that quantifies the degree to which a gene expression value is impacted by CNAs and leveraged this analysis at the pathway level. Our results show that a...

Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, long...

High-grade serous carcinoma (HGSC) remains the deadliest gynecological cancer, mostly due to the widespread metastases in abdominal cavities already at diagnosis. To improve therapy success, understanding metastasis routes and their molecular characteristics is crucial. Herein, we used >400 samples subjected to whole-genome bisulfite (WGBS) and RNA...

Ovarian high-grade serous carcinoma (HGSC) represents the deadliest gynecological malignancy, with 10-15% of patients exhibiting primary resistance to first-line chemotherapy. These primarily chemo-refractory patients have particularly poor survival outcomes, emphasizing the urgent need for developing predictive biomarkers and novel therapeutic app...

DNA methylation plays a critical role in tumor progression and response to chemotherapy. Frequently dysregulated during tumor development, it is closely intertwined with mixed effects from patient epigenetic background, tissue context, and treatment pressure. Here, we leveraged methylomic and transcriptomic profiling of 400 whole-genome sequencing...

The evolution of tumors from diagnosis to relapse in ovarian high-grade serous carcinoma (HGSC) patients is poorly understood. Consequently, it is unknown whether diagnostic samples are representative enough to guide treatment directions at relapse, or whether acquired changes during therapy provide targets in patients with relapses. To answer thes...

High-grade serous ovarian cancer (HGSC) is the most frequent and lethal ovarian cancer type. Despite responding favorably to first-line therapy, most HGSC patients eventually relapse. HGSC is characterized by high interpatient genomic heterogeneity and few recurrent mutations that could be used as therapeutic biomarkers. Thus, except the introducti...

Background: Copy-number alterations (CNAs) are a key hallmark of cancer and play a major role in chemotherapy resistance. Earlier studies aiming to identify genes with CNA-associated expression levels do not explicitly quantify the degree of CNA regulation on expression levels, leading to an overabundance of false positive discoveries. To overcome...

Ovarian high-grade serous carcinoma (HGSC) is commonly diagnosed at an advanced stage, showing multiple genetically heterogeneous clones existing prior to therapeutic intervention. Most of the patients respond well to primary therapy, but cancer relapses within few years and develops treatment resistance. Genomics changes in tumors during therapy a...

To characterize the role of DNA methylation (DNAm) in chemotherapy response, we analyzed whole-genome DNAm data integrated with transcriptome from 67 samples of 17 patients with ovarian high grade serous carcinoma (HGSC) belonging to the prospective, longitudinal, multi-region DECIDER trial (NCT04846933). We used a novel decomposition method, which...

Background: Visualization is an indispensable facet of genomic data analysis. Despite the abundance of specialized visualization tools, there remains a distinct need for tailored solutions. However, their implementation typically requires extensive programming expertise from bioinformaticians and software developers, especially when building intera...

Detecting cell types from histopathological images is essential for various digital pathology applications. However, large number of cells in whole-slide images (WSIs) necessitates automated analysis pipelines for efficient cell type detection. Herein, we present hematoxylin and eosin (H&E) Image Processing pipeline (HEIP) for automatied analysis o...

Introduction/Background Neoadjuvant chemotherapy (NACT) is the preferred treatment strategy for high-grade serous (ovarian) cancer (HGSC) patients, if optimal cytoreduction is estimated unachievable at the time of the diagnosis. In such cases, intrinsic sensitivity to standard-of-care (platinum and taxane combination therapy) is a major determinant...

Introduction/Background Ovarian high-grade serous carcinoma (HGSC) is commonly diagnosed at an advanced stage, showing multiple genetically heterogeneous clones existing prior to therapeutic intervention. Methodology Clonal composition and topology were estimated from whole-genome sequencing data from 510 samples of 148 patients in the prospective...

The broad research use of organoids from high-grade serous ovarian cancer (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here, we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (53% vs. 23%-38%). We established...

Neoadjuvant chemotherapy (NACT) is the preferred treatment strategy for high-grade serous (ovarian) cancer (HGSC) patients, if optimal cytoreduction is estimated unachievable at the time of the diagnosis. In such cases, intrinsic sensitivity to standard-of-care (platinum and taxane combination therapy) is a major determinant of the disease progress...

High-grade serous ovarian cancer (HGSC) is the most prevalent and lethal ovarian cancer type. While HGSC usually responds well to primary treatment, most cases eventually relapse. Functional precision medicine - tailoring individualized treatments based on functional in vitro assays on patient-derived cells - has been recently employed in cancer cl...

Homologous recombination DNA-repair deficiency (HRD) is a common driver of genomic instability and confers a therapeutic vulnerability in cancer. The accurate detection of somatic allelic imbalances (AIs) has been limited by methods focused on BRCA1/2 mutations and using mixtures of cancer types. Using pan-cancer data, we revealed distinct patterns...

L1 retrotransposons are the only protein-coding active transposable elements in the human genome. Although silenced during normal conditions, they are highly expressed in human epithelial cancers including high-grade serous ovarian cancer (HGSC), where they transcribe to form L1 mRNA and subsequently integrate into the genome by a process called re...

Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we characterized HGSC evolutionary states using whole-genome sequencing data from 214 samples of 55 HGSC patients in the prospective, longitudinal,...

Extensive utilization of organoids from high-grade serous ovarian carcinoma (HGSOC), the most common and lethal ovarian cancer, has been hampered by low success rates of long-term culture and scarcity of fresh tumor material. Here we present the development of a novel method for efficient generation, expansion and use of HGSOC organoids from cryopr...

High-grade serous ovarian cancer (HGSC) is the most common form of epithelial ovarian cancer, typically diagnosed at advanced stage with five-year survival of only 38%. Herein, we used 149 treatment-naïve and 65 after-treatment samples subjected to whole-genome sequencing from 55 HGSC patients to reconstruct evolutionary histories, characterize clo...

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR003) of the Conference Proceedings. Citation Format: Alexandra Lahtinen, Kari Lavikka, Yilin Li, Sanaz Jamalzadeh, Anni Virtanen, Rainer Lehtonen, Olli Carpén, Sakari Hietanen, Kaisa Huhtinen, Antti Häkkinen...

The broad research use of organoids from high-grade serous ovarian carcinoma (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (55% vs. 23-38%). We established...

Current genome browsers have rigid visualization capabilities and depend on specific file formats. We present a declarative, grammar-based approach for building interactive genomic visualizations and demonstrate its utility with two case studies involving high-grade serous ovarian cancer data.

PURPOSE Circulating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here,...

Anduril is an analysis and integration framework that facilitates the design, use, parallelization and reproducibility of bioinformatics workflows. Anduril has been upgraded to use Scala for pipeline construction, which simplifies software maintenance, and facilitates design of complex pipelines. Additionally, Anduril's bioinformatics repository ha...