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Zenklusen, J. C.

Publications and source records attributed to Zenklusen, J. C..

2 recordsLinked to original sources

Just Add Data: Automated Predictive Modeling and BioSignature Discovery

Fully automated machine learning, statistical modelling, and artificial intelligence for predictive modeling is becoming a reality, giving rise to the field of Automated Machine Learning (AutoML). AutoML systems promise to democratize data analysis to non-experts, drastically increase productivity, improve replicability of the statistical analysis, facilitate the interpretation of results, and shield against common methodological analysis pitfalls. We present the basic ideas and principles of Just Add Data Bio (JADBIO), an AutoML technology applicable to the low-sample, high-dimensional omics data that arise in translational medicine and bioinformatics applications. In addition to predictive and diagnostic models ready for clinical use, JADBIO also returns the corresponding biosignatures, i.e., minimal-size subsets of biomarkers that are jointly predictive of the outcome of interest. A use-case on thymic epithelial tumors is presented, along with an extensive evaluation on 374 public biological datasets. Results show that long-standing challenges with overfitting and overestimation of complex non-linear machine learning pipelines on high-dimensional, low small sample data can be overcome.

bioinformatics

Distinct epigenetic shift in a subset of Glioma CpG island methylator phenotype (G-CIMP) during tumor recurrence

Histomorphology and current grading schemes are unable to predict glioma relapse and malignant tumor progression. We reported that the IDH-mutant associated Glioma-CpG Island Methylator Phenotype (G-CIMP) can be further divided into two clinically distinct subtypes independent of histopathological grading (G-CIMP-high and -low) with evidence of correlation with tumor progression. Here we performed a comprehensive epigenomic analysis of 74 longitudinally collected glioma samples (grade II-IV) to understand malignant recurrence from G-CIMP-high to G-CIMP-low. G-CIMP-low recurrence appeared in 12% of all gliomas and resemble IDH-wildtype primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, stem cell-like epigenomic phenotype, and genomic instability. Finally, we defined a set of candidate biomarker signatures that predict recurrence of G-CIMP-low with clinically relevance on patient outcomes. Our study provides opportunity for refined clinical trial designs and therapeutic targets that limit progression to more aggressive G-CIMP-low phenotype.\n\nHIGHLIGHTSO_LIIndolent G-CIMP-high progresses to aggressive G-CIMP-low phenotype\nC_LIO_LIIncidence of G-CIMP-low recurrent tumors are 3 times greater than G-CIMP-low primary\nC_LIO_LIG-CIMP-low recurrent tumors share epigenomic features with IDH-wildtype primary GBM\nC_LIO_LIPredictive biomarkers of G-CIMP-low progression at primary diagnosis\nC_LI

cancer biology