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Colloquium STIMULATE


Speaker:           Wolfgang M. A. Pernice, Ph.D., Columbia University, Departement of Neurology

Title:                  Deep learning for the rapid detection of disease-associated phenotypes in primary cell-culture models through high-content morphological profiling

Date/Time:     August 09, 2018, at 3:30 p.m.

Where:            In the historic hall of the Guericke Centrum



Despite abundant sequencing data, our understanding of the genetic landscape of neurodegenerative diseases remains woefully incomplete. While gene discovery studies typically result in numerous candidates, traditional gene-by-gene strategies for experimental validation quickly become infeasible at scale. We hence sought to develop an unbiased, high-content approach to a) rapidly screen patient derived cells for distinguishing phenotypes that allow the experimental validation of candidate genetic variants and that b) allows inference of sufficient biological context to enable targeted follow-up studies for genes with unknown function. We here apply supervised machine learning methods as an unbiased, high-content approach to mine high-resolution, multiplexed fluorescent microscopy images of individual cells in primary culture, for distinguishing (testable) morphological phenotypes, that allow their classification according to genotype. In a prototype study we demonstrate that this approach can a) achieve super-human classification accuracy, b) allows for rapid phenotypic evaluation of cells with mutations unbeknownst to the network, and we pioneer its application to primary cells derived from patients with neurodegenerative conditions.


Curriculum Vitae

Dr. Pernice completed his undergraduate studies at Imperial College London. In 2016 he obtained his Ph.D. in Cell Biology and Molecular Medicine from Columbia University. As a graduate student in the lab of Dr. Liza Pon, Dr. Pernice focused on the identification of novel mitochondrial tethering mechanisms that control mitochondrial quality and inter-organellar exchange of metabolites in the budding yeast S. cerevisiae and mammalian organisms.

Dr. Pernice is currently a postdoctoral fellow in the laboratory of Dr. Michio Hirano at Columbia University Medical Center and joint fellow with the Inherited Neuropathy Consortium (INC) and North-American Mitochondrial Disease consortium (NAMDC). In Dr. Hirano’s group, Dr. Pernice focusses on the development of tools for biological image-mining based on supervised artificial intelligence systems, that can be applied to clinical diagnostics and the identification and characterization of novel disease genes in neurodegenerative conditions.

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