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Kersten, N.

Publications and source records attributed to Kersten, N..

2 recordsLinked to original sources

Multi-view confounder detection for biomedical studies

In many biomedical studies an important first step is checking for confounding factors. For association studies, confounding can for example be caused by ethnic differences in the case and control groups. In many other settings there might be confounding factors like batch effects or founder effects that also need to be detected and controlled for1. Detecting confounding for data from one data source is well established (e.g., genomics data). Since more and more studies are now based on data from multiple data modalities (e.g., multi-omics), we evaluated whether multi-view confounder detection can benefit from state-of-the-art methods for multi-view data integration. Especially for clustering of multi-omics data, it has been shown that these methods can perform better than methods that treat the data modalities separately2. Our results show that multi-view confounder analysis is possible and that building on multi-view data integration methods is better than treating the different data modalities separately.

bioinformatics↗

Protein profiling of breast carcinomas reveals expression of immune-suppressive factors and signatures relevant to patient outcome

BackgroundIn cancerous tissue, a complex interplay of tumour cells with different cell types from the tumour microenvironment is causing modulations in signalling processes. By directly assessing expression of a multitude of proteins and protein variants, extensive information on signalling pathways, their activation status and the effect of the immunological landscape can be obtained providing viable information for treatment response. MethodsProtein extracted from archived breast cancer tissue from patients without adjuvant therapy was subjected to high-throughput Western blotting using the DigiWest technology. Expression of 150 proteins and protein variants covering cell cycle control, apoptosis, Jak/Stat, MAPK-, Pi3K/Akt-, Wnt-, and, autophagic signalling as well as general tumour markers was monitored in a cohort of 84 patient samples. The degree of immune cell infiltration was investigated and set against treatment outcome by integrating patient specific follow-up data. ResultsCharacterization of the tumour microenvironment by monitoring CD8, CD11c, CD16 and CD68 expression revealed a strong correlation of event-free patient survival with immune cell infiltration. Furthermore, the presence of tumour infiltrating lymphocytes was linked to a pronounced activation of the Jak/Stat signalling pathway and apoptotic processes. Elevated phosphorylation of peroxisome proliferator-activated receptor gamma (PPAR{gamma}, pS112) in non-immune infiltrated tumour tissue suggests a novel immune evasion mechanism in breast cancer characterized by increased PPAR{gamma} activation. ConclusionMultiplexed immune cell marker assessment and protein profiling of tumour tissue provides functional signalling data facilitating breast cancer patient stratification.

cancer biology↗