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Temporal Changes in Functional Gene Group Expression Occur Early in Alzheimer`s Disease Progression. Shahar Barbash And Prof Hermona Soreq. Research question. Disease processes. Early events. Disease progression. Late events. Which events are late and which events are early?.
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Temporal Changes in Functional Gene Group Expression Occur Early in Alzheimer`s Disease Progression ShaharBarbashAnd Prof HermonaSoreq
Research question Disease processes Early events Disease progression Late events Which events are late and which events are early? Barbash & Soreq
Research question What would be a relevant disease event - single key transcripts or gene groups? 1 Which events are late and which events are early? 2 Barbash & Soreq
Analyzed Data Sets Hip Incipient, 20<MMSE<25 Moderate, 15<MMSE<20 Severe, MMSE<15 Hip, EC, PVC Barbash & Soreq
Analysis Approach Small number of large changes Large number of small changes Barbash & Soreq
What would be a relevant disease event – single transcripts or gene groups? 1 Barbash & Soreq
What is a Relevant Disease Event? IGD: Inter-group Dissimilarity LCM: Laser-captured Micro- dissection Barbash & Soreq
Cognitive State Identifies Gradual Shifts in: cell type and sub-cellular specific transcripts biological processes Barbash & Soreq
Gene groups reflect hippocampal alterations in AD better than single genes What is a relevant disease event? 1 Change in gene group expression. Which are late events and which are early events? 2 Barbash & Soreq
Different Hippocampcal Processes Show Distinct AD Dynamics Barbash & Soreq
Conclusions • Gene groups reflect hippocampal alterations in AD better than single genes • Some processes are altered early while some are altered late in the disease Barbash & Soreq
Acknowledgments PhD Supervisor: Prof Hermona Soreq Lab members: Dr. David Greenberg Dr. Estelle R. Bennett Keren Ailon Mor Hanan Geula Hanin Nir Waiskopf Lilach Soreq Yael Goll Uriya Bekenstein Nadav Yayon The Eric Roland Center for Neurodegenerative Diseases
End Barbash & Soreq
Distribution comparisons • Global expression ratio between AD and control. • Down regulated functional group. • Up regulated functional group. • Tightly regulated functional group. Kolmogorov-Smirnov (KS) Barbash & Soreq
AD involves alterations in gene groupsbut not single genes Barbash & Soreq
Cognitive measure identified gradual shifts in microRNAs population mirRor:Friedman Y et al, Bioinformatics,2010 Barbash & Soreq