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Chatzaki, E.

Publications and source records attributed to Chatzaki, E..

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↗

Development of the MAM model of schizophrenia in mice: Sex similarities and differences of prefrontal cortical and hippocampal function

Schizophrenia is a debilitating disorder with complex and unclarified etiological factors. Sex differences have been observed in humans but animal models have only focused on male subjects. In this study, we report the establishment of the neurodevelopmental MAM model of schizophrenia in mice and compare the schizotypic-like characteristics and cognitive function in both sexes. Pregnant mice were injected with 26mg/kg(i.p.) of Methylazoxy-methanol acetate (MAM) or saline (5ml/kg) on gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Behavioral, histological and electrophysiological and mass spectrometry-based comparative proteomic techniques were employed to assess the schizotypic-like characteristics and cognitive function of adult male and female offspring (MAM- or saline-treated). Female MAM-16, but not MAM-17 treated mice exhibited enhanced hyperlocomotion after acute administration of the NMDA receptor antagonist, MK-801, compared to saline treated mice. Male MAM-16, but not MAM-17 treated mice showed decreased pre-pulse inhibition of the acoustic startle reflex. Both male and female MAM-16 and MAM-17 treated mice exhibited reduced hippocampal (HPC) size and thinning of the prefrontal cortex (PFC), but only male MAM-16 treated mice showed decreased parvalbumin expression in HPC and PFC. Similarly, both male and female MAM-16 treated mice displayed impaired contextual fear memory, while only male MAM-16 treated mice exhibited deficits in the delayed alternation task. The neurophysiological mechanisms that underlie these cognitive functions were further investigated. Both male and female MAM-16 treated mice had significantly reduced long-term potentiation (LTP) in the HPC CA1 synapses, while only male MAM-16 treated mice exhibited decreased LTP in the PFC. Proteomic analyses of PFC lysates further showed significant MAM- and sex-dependent differences in regulation of protein expression. Our results demonstrate that while both male and female mice, prenatally exposed to MAM on GD16, display several core schizophrenia-like deficits and impairments in the hippocampus, only male MAM-treated mice have PFC-dependent cognitive deficits.

neuroscience↗