| 1. |
- Bergholtz, Helga, et al.
(author)
-
Contrasting DCIS and invasive breast cancer by subtype suggests basal-like DCIS as distinct lesions
- 2020
-
In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
-
Journal article (peer-reviewed)abstract
- Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer with highly variable potential of becoming invasive and affecting mortality. Currently, many patients with DCIS are overtreated due to the lack of specific biomarkers that distinguish low risk lesions from those with a higher risk of progression. In this study, we analyzed 57 pure DCIS and 313 invasive breast cancers (IBC) from different patients. Three levels of genomic data were obtained; gene expression, DNA methylation, and DNA copy number. We performed subtype stratified analyses and identified key differences between DCIS and IBC that suggest subtype specific progression. Prominent differences were found in tumors of the basal-like subtype: Basal-like DCIS were less proliferative and showed a higher degree of differentiation than basal-like IBC. Also, core basal tumors (characterized by high correlation to the basal-like centroid) were not identified amongst DCIS as opposed to IBC. At the copy number level, basal-like DCIS exhibited fewer copy number aberrations compared with basal-like IBC. An intriguing finding through analysis of the methylome was hypermethylation of multiple protocadherin genes in basal-like IBC compared with basal-like DCIS and normal tissue, possibly caused by long range epigenetic silencing. This points to silencing of cell adhesion-related genes specifically in IBC of the basal-like subtype. Our work confirms that subtype stratification is essential when studying progression from DCIS to IBC, and we provide evidence that basal-like DCIS show less aggressive characteristics and question the assumption that basal-like DCIS is a direct precursor of basal-like invasive breast cancer.
|
|
| 2. |
- Bolin, David, 1983, et al.
(author)
-
Calibrating regionally downscaled precipitation over Norway through quantile-based approaches
- 2016
-
In: Advances in Statistical Climatology, Meteorology and Oceanography. - 2364-3579 .- 2364-3587. ; 2, s. 39-47
-
Journal article (peer-reviewed)abstract
- Dynamical downscaling of earth system models is intended to produce high-resolution climate in- formation at regional to local scales. Current models, while adequate for describing temperature distributions at relatively small scales, struggle when it comes to describing precipitation distributions. In order to better match the distribution of observed precipitation over Norway, we consider approaches to statistical adjustment of the output from a regional climate model when forced with ERA-40 reanalysis boundary conditions. As a second step, we try to correct downscalings of historical climate model runs using these transformations built from downscaled ERA-40 data. Unless such calibrations are successful, it is difficult to argue that scenario-based downscaled climate projections are realistic and useful for decision makers. We study both full quantile cali- brations and several different methods that correct individual quantiles separately using random field models. Results based on cross-validation show that while a full quantile calibration is not very effective in this case, one can correct individual quantiles satisfactorily if the spatial structure in the data are accounted for. Interestingly, different methods are favoured depending on whether ERA-40 data or historical climate model runs are adjusted.
|
|
| 3. |
- Fleischer, Thomas, et al.
(author)
-
Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis
- 2014
-
In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:8, s. 435-
-
Journal article (peer-reviewed)abstract
- Background: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results: We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma. Conclusions: This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.
|
|
| 4. |
- Sandve, Geir K., et al.
(author)
-
The differential disease regulome
- 2011
-
In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Transcription factors in disease-relevant pathways represent potential drug targets, by impacting a distinct set of pathways that may be modulated through gene regulation. The influence of transcription factors is typically studied on a per disease basis, and no current resources provide a global overview of the relations between transcription factors and disease. Furthermore, existing pipelines for related large-scale analysis are tailored for particular sources of input data, and there is a need for generic methodology for integrating complementary sources of genomic information.Results: We here present a large-scale analysis of multiple diseases versus multiple transcription factors, with a global map of over-and under-representation of 446 transcription factors in 1010 diseases. This map, referred to as the differential disease regulome, provides a first global statistical overview of the complex interrelationships between diseases, genes and controlling elements. The map is visualized using the Google map engine, due to its very large size, and provides a range of detailed information in a dynamic presentation format.The analysis is achieved through a novel methodology that performs a pairwise, genome-wide comparison on the cartesian product of two distinct sets of annotation tracks, e.g. all combinations of one disease and one TF.The methodology was also used to extend with maps using alternative data sets related to transcription and disease, as well as data sets related to Gene Ontology classification and histone modifications. We provide a web-based interface that allows users to generate other custom maps, which could be based on precisely specified subsets of transcription factors and diseases, or, in general, on any categorical genome annotation tracks as they are improved or become available.Conclusion: We have created a first resource that provides a global overview of the complex relations between transcription factors and disease. As the accuracy of the disease regulome depends mainly on the quality of the input data, forthcoming ChIP-seq based binding data for many TFs will provide improved maps. We further believe our approach to genome analysis could allow an advance from the current typical situation of one-time integrative efforts to reproducible and upgradable integrative analysis. The differential disease regulome and its associated methodology is available at © 2011 Sandve et al; licensee BioMed Central Ltd.
|
|
| 5. |
- Sandve, Geir K., et al.
(author)
-
The Genomic HyperBrowser: Inferential genomics at the sequence level
- 2010
-
In: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1474-760X .- 1465-6906. ; 11
-
Journal article (peer-reviewed)abstract
- The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack of established methodology with the required flexibility and power. We propose a first principled approach to statistical analysis of sequence-level genomic information. We provide a growing collection of generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along the genome. The Genomic HyperBrowser implements the approach and is available at http://hyperbrowser.uio.no.© 2010 Sandve et al.; licensee BioMed Central Ltd.
|
|
| 6. |
- Tekpli, Xavier, et al.
(author)
-
An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Journal article (peer-reviewed)abstract
- How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast cancer gene expression datasets, we invariably identify three clusters of patients with gradual levels of immune infiltration. The intermediate immune infiltration cluster (Cluster B) is associated with a worse prognosis independently of known clinicopathological features. Furthermore, immune clusters are associated with response to neoadjuvant chemotherapy. In silico dissection of the immune contexture of the clusters identified Cluster A as immune cold, Cluster C as immune hot while Cluster B has a pro-tumorigenic immune infiltration. Through phenotypical analysis, we find epithelial mesenchymal transition and proliferation associated with the immune clusters and mutually exclusive in breast cancers. Here, we describe immune clusters which improve the prognostic accuracy of immune contexture in breast cancer. Our discovery of a novel independent prognostic factor in breast cancer highlights a correlation between tumor phenotype and immune contexture.
|
|
| 7. |
- Villani, Antonella, et al.
(author)
-
A Characterization of Internet Dating Network Structures among Nordic Men Who Have Sex with Men
- 2012
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:7
-
Journal article (peer-reviewed)abstract
- Background: The Internet has become an important venue for seeking sexual partners and may facilitate transmission of sexually transmitted infections. Methods: We examined a 64-day data log of flirt messages expressing sexual interest among MSM within the Qruiser. com community. We used logistic regression to analyze characteristics of MSM sending and receiving flirt messages and negative binomial regression to examine individual activity and popularity. The structural properties, including the core structure of the flirt network, were analyzed. Results: The MSM population consisted of approximately 40% homosexuals and 37% bisexuals, while the remaining 23% included men who identified as heterosexual but searched for sex with men and experimental. MSM were more likely to send flirt messages if they were homosexual and aged 40+ years; young people aged, 30 years were more likely to receive a flirt. Possession of a webcam was strongly associated with both sending flirt messages and being a flirt target. The distributions of flirts sent (max k(out) = 2162) and received (max k(in) = 84) were highly heterogeneous. Members in central cores were more likely homosexuals, singles, and aged 31-40 years. The probability of a matched flirt (flirt returned from target) increased from 1% in the outer core to 18% in the central core (core size = 4). Discussion: The flirt network showed high degree heterogeneity similar to the structural properties of real sexual contact networks with a single central core. Further studies are needed to explore use of webcam for Internet dating.
|
|
