Tonje G. Lien

ORCID: 0000-0003-3331-4201
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About
Contact & Profiles
Research Areas
  • Gene expression and cancer classification
  • Bioinformatics and Genomic Networks
  • Cancer Genomics and Diagnostics
  • Breast Cancer Treatment Studies
  • Genomics and Chromatin Dynamics
  • Statistical Methods and Inference
  • Cancer Cells and Metastasis
  • Radiomics and Machine Learning in Medical Imaging
  • Genetics, Bioinformatics, and Biomedical Research
  • Epigenetics and DNA Methylation
  • Cancer Immunotherapy and Biomarkers
  • MicroRNA in disease regulation
  • Genetic Mapping and Diversity in Plants and Animals
  • Genetic Associations and Epidemiology
  • HER2/EGFR in Cancer Research
  • Chromosomal and Genetic Variations
  • Advanced Breast Cancer Therapies
  • Genomics and Phylogenetic Studies
  • RNA and protein synthesis mechanisms
  • Cancer-related molecular mechanisms research
  • Digital Radiography and Breast Imaging
  • Veterinary Oncology Research
  • Gastric Cancer Management and Outcomes
  • Breast Lesions and Carcinomas
  • Metastasis and carcinoma case studies

Oslo University Hospital
2014-2025

Norwegian Cancer Society
2023

University of Oslo
2013-2018

Cancer Genetics (United States)
2018

University of Bergen
2013

Norwegian Computing Center
2013

Norwegian University of Science and Technology
2013

How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast gene expression datasets, we invariably identify three clusters patients gradual levels infiltration. The intermediate infiltration cluster (Cluster B) associated a worse prognosis independently known clinicopathological features. Furthermore, are response to neoadjuvant chemotherapy. silico dissection the contexture identified Cluster A as cold, C hot while B has...

10.1038/s41467-019-13329-5 article EN cc-by Nature Communications 2019-12-03

For many high‐dimensional studies, additional information on the variables, like (genomic) annotation or external p ‐values, is available. In context of binary and continuous prediction, we develop a method for adaptive group‐regularized (logistic) ridge regression, which makes structural use such ‘co‐data’. Here, ‘groups’ refer to partition variables according co‐data. We derive empirical Bayes estimates group‐specific penalties, possess several nice properties: (i) They are analytical....

10.1002/sim.6732 article EN Statistics in Medicine 2015-09-13

The aim of this study was to investigate the prognostic value PAM50 intrinsic subtypes and risk recurrence (ROR) score in patients with early breast cancer long-term follow-up. A special focus placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 not treated chemotherapy.Patients (n = 653) enrolled observational Oslo1 (1995-1998) were followed for distant death. Clinicopathological parameters collected from hospital records. primary tumors...

10.1186/s13058-017-0911-9 article EN cc-by Breast Cancer Research 2017-11-14

Multigene assays for molecular subtypes and biomarkers can aid management of early invasive breast cancer. Using RNA-sequencing we aimed to develop single-sample predictor (SSP) models clinical markers, subtypes, risk recurrence (ROR). A cohort 7743 patients was divided into training test set. We trained SSPs ROR assigned by nearest-centroid (NC) methods from histopathology. Classifications were compared with Prosigna in two external cohorts (ABiM, n = 100 OSLO2-EMIT0, 103). Prognostic value...

10.1038/s41523-022-00465-3 article EN cc-by npj Breast Cancer 2022-08-16

Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand organizational principles regulating human genome. Here, we use chromosome-chromosome contact as knowledge-based constraints for large-scale three-dimensional diploid The resulting remain minimally entangled and acquire several functional features that are observed in vivo were never used input model. We find, instance, gene-rich, active regions drawn towards nuclear center, while...

10.1038/srep35985 article EN cc-by Scientific Reports 2016-10-27

DNA methylation affects expression of associated genes and may contribute to the missing genetic effects from genome-wide association studies osteoporosis. To improve insight into mechanisms postmenopausal osteoporosis, we combined transcript profiling with analyses in bone. RNA were isolated 84 bone biopsies donors varying markedly mineral density (BMD). In all, 2529 CpGs top 100 most significantly BMD analyzed. The levels at 63 differed between healthy osteoporotic women 10% false...

10.1080/15592294.2017.1345832 article EN Epigenetics 2017-06-26

Abstract Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer with highly variable potential becoming invasive and affecting mortality. Currently, many patients DCIS are overtreated due to the lack specific biomarkers that distinguish low risk lesions from those higher progression. In this study, we analyzed 57 pure 313 cancers (IBC) different patients. Three levels genomic data were obtained; gene expression, DNA methylation, copy number. We performed subtype stratified...

10.1038/s41523-020-0167-x article EN cc-by npj Breast Cancer 2020-06-17

Abstract During breast tumor progression, the transition from ductal carcinoma in situ (DCIS) to invasive cancer is a critical step with large implications for prognosis. However, mechanisms of invasion are still largely unknown. At DCIS stage, there an over-representation HER2-positive lesions compared cancer. In this study, we investigated associations between gene expression profiles cells and immune microenvironment tumors concurrent using spatial transcriptomics. We found distinctly...

10.1186/s13058-025-01990-2 article EN cc-by Breast Cancer Research 2025-03-21

Abstract Summary: Recently developed methods that couple next-generation sequencing with chromosome conformation capture-based techniques, such as Hi-C and ChIA-PET, allow for characterization of genome-wide chromatin 3D structure. Understanding the organization in three dimensions is a crucial next step unraveling global gene regulation, analyzing data are needed. We have HiBrowse, user-friendly web-tool consisting range hypothesis-based descriptive statistics, using realistic assumptions...

10.1093/bioinformatics/btu082 article EN cc-by-nc Bioinformatics 2014-02-07

The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, are faced with challenge how best analyze interpret their genome-scale datasets. A powerful way representing data is feature-specific coordinates relative reference genome assemblies, i.e. tracks. Genomic HyperBrowser...

10.1093/nar/gkt342 article EN cc-by Nucleic Acids Research 2013-04-30

Abstract Breast cancers in humans belong to one of several intrinsic molecular subtypes each with different tumor biology and clinical impact. Mammary gland tumors dogs are proposed as a relevant comparative model for human breast cancer; however, it is still unclear whether the have same significance humans. Using publicly available data, we analyzed gene expression whole-exome sequencing data from 158 canine mammary tumors. We performed subtyping using PAM50 method followed by...

10.1007/s10911-022-09523-9 article EN cc-by Journal of Mammary Gland Biology and Neoplasia 2022-06-01

The study of chromatin 3D structure has recently gained much focus owing to novel techniques for detecting genome-wide contacts using next-generation sequencing. A deeper understanding the architecture DNA inside nucleus is crucial gaining insight into fundamental processes such as transcriptional regulation, genome dynamics and stability. Chromatin conformation capture-based methods, Hi-C ChIA-PET, are now paving way routine studies in a range organisms tissues. However, appropriate methods...

10.1093/nar/gkt227 article EN Nucleic Acids Research 2013-04-08

Abstract Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers improved response lacking. Here, we report on randomized phase II clinical trial study the added effect bevacizumab in FEC100 (5‐fluorouracil, epirubicin and cyclophosphamide) taxanes ( n = 132 patients). Gene expression from tumors was obtained before treatment, treatment...

10.1002/ijc.33108 article EN cc-by-nc International Journal of Cancer 2020-06-03

Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer with highly variable potential becoming invasive and affecting mortality the patients. Due to lack accurate markers disease progression, many women detected DCIS are currently overtreated. To distinguish those cases who likely require therapy from should be left untreated, there need for robust predictive biomarkers extracted molecular or genetic profiles. We developed supervised machine learning approach that implements...

10.3389/fgene.2021.670749 article EN cc-by Frontiers in Genetics 2021-06-03

The PAM50 gene expression subtypes and the associated risk of recurrence (ROR) score are used to predict benefits adjuvant therapy in early-stage breast cancer. Prosigna assay includes along with their clinicopathological features, is approved for treatment recommendations hormonal chemotherapy hormone-receptor-positive early test utilizes RNA extracted from macrodissected tumor cells obtained formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, fresh-frozen (FF) bulk without...

10.3390/cancers13236118 article EN Cancers 2021-12-04

Using high-dimensional penalized regression we studied genome-wide DNA-methylation in bone biopsies of 80 postmenopausal women relation to their mineral density (BMD). The showed BMD varying from severely osteoporotic normal. Global gene expression data the same individuals was available, and since often affects expression, overall aim this paper include both these omics sets into an integrated analysis. classical uses one penalty, but incorporated individual penalties for each sites. These...

10.1186/s12920-018-0341-2 article EN cc-by BMC Medical Genomics 2018-03-07

Unsupervised clustering is important in disease subtyping, among having other genomic applications. As data has become more multifaceted, how to cluster across sources for precise subtyping an ever area of research. Many the methods proposed so far, including iCluster and Cluster Assignments (COCAs), make unreasonable assumption a common all sources, those that do not are fewer tend be computationally intensive.We propose Bayesian parametric model integrative, unsupervised sources. In our...

10.1093/bioinformatics/btz381 article EN Bioinformatics 2019-05-01

Abstract Up to 50% of patients diagnosed with ductal carcinoma in situ (DCIS) never experience progression invasive disease, even if left untreated. Current knowledge what makes DCIS become is limited and we lack diagnostic tools predict which can be spared treatment. Escape tumor cells from the breast ducts influenced by characteristics cells, microenvironment surrounding ducts, interplay between two. Intraductal are not physically contact extraductal stromal cells. Until now, analyses...

10.1158/1538-7445.advbc23-pr05 article EN Cancer Research 2024-02-01

Abstract Background Identifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide powerful tool for studying these. Assuming Gaussian graphical model, association may be estimated from multiomic data the non-zero entries inverse covariance matrix. Inferring such biological networks challenging because high dimensionality problem, making traditional estimators unsuitable. The lasso constructed estimation sparse matrices situations,...

10.1186/s12859-021-04413-z article EN cc-by BMC Bioinformatics 2021-10-15

High mammographic density (MD) is associated with a 4–6 times increase in breast cancer risk. For post-menopausal women, MD often decreases over time, but little known about the underlying biological mechanisms. reflects tissue composition, and may be microenvironment subtypes previously identified tumor-adjacent normal tissue. Currently, these have not been explored We obtained biopsies from breasts of healthy women at two different time points several years apart performed microarray gene...

10.1007/s10911-018-09423-x article EN cc-by Journal of Mammary Gland Biology and Neoplasia 2019-01-06

ABSTRACT Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand organizational principles regulating human genome. Here, we use chromosome-chromosome contact as knowledge- based constraints for large-scale three-dimensional diploid The resulting remain minimally entangled and acquire several functional features that are observed in vivo were never used input model. We find, instance, gene-rich, active regions drawn towards nuclear...

10.1101/079558 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2016-10-17

Abstract Motivation Unsupervised clustering is important in disease subtyping, among having other genomic applications. As data has become more multifaceted, how to cluster across sources for precise subtyping an ever area of research. Many the methods proposed so far, including iCluster and Cluster Assignments, make unreasonble assumption a common all sources, those that do not are fewer tend be computationally intensive. Results We propose Bayesian parametric model integrative,...

10.1101/387076 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2018-08-07

ABSTRACT Background Multigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer (IBC). Based on RNA-sequencing we aimed to develop robust single-sample predictor (SSP) models conventional markers as well intrinsic subtype risk recurrence (ROR) that provide clinically relevant prognostic stratification. Methods A uniformly accrued cohort 7743 patients with data from fresh tissue was divided into a training set (n=5250) reserved...

10.1101/2021.12.03.21267116 preprint EN cc-by medRxiv (Cold Spring Harbor Laboratory) 2021-12-05
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