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DTSTART;TZID=America/Los_Angeles:20210528T110000
DTEND;TZID=America/Los_Angeles:20210528T113000
DTSTAMP:20260518T040927
CREATED:20210512T184047Z
LAST-MODIFIED:20210601T154745Z
UID:18164-1622199600-1622201400@qcb.ucla.edu
SUMMARY:QCBio Research Seminar: Yi Ding (Pasaniuc)
DESCRIPTION:TITLE: “Large uncertainty in individual PRS estimation impacts PRS-based risk stratification.”\nABSTRACT: Large-scale genome-wide association studies have enabled polygenic risk scores (PRS)\, which estimate the genetic value of an individual for a given trait. Since PRS accuracy is typically assessed using cohort-level metrics\, uncertainty in PRS estimates at individual level remains underexplored. In this talk\, we will first introduce a Bayesian framework that can estimate the variance of an individual’s PRS and can yield well-calibrated credible intervals for the genetic value of a single individual. Then we will discuss the impact of PRS uncertainty on risk stratification and present a probabilistic PRS-based risk stratification approach to incorporate the uncertainty in individual PRS estimates. Finally\, we’ll present a theoretical estimate of individual PRS variance as a function of heritability\, number of causal SNPs and sample size.\n\nhttps://qcb.ucla.edu/wp-content/uploads/sites/14/2021/05/Yi-Ding-edited.mp4
URL:https://qcb.ucla.edu/event/qcbio-research-seminar-yi-ding-pasaniuc/
LOCATION:ZOOM\, CA\, United States
CATEGORIES:Research Seminars
ATTACH;FMTTYPE=image/jpeg:https://wp-misc.lifesci.ucla.edu/qcb/wp-content/uploads/sites/14/2021/05/Yi-Ding.jpg
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DTSTART;TZID=America/Los_Angeles:20210528T110000
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DTSTAMP:20260518T040927
CREATED:20210520T191323Z
LAST-MODIFIED:20210527T021150Z
UID:18199-1622199600-1622201400@qcb.ucla.edu
SUMMARY:QCBio Research Seminar: Jakob Von Morgenland (Venugopal)
DESCRIPTION:TITLE: “Constructing a Functional Interactome from Published Work to Identify Underrepresented and Integrative Effects of Neuroinflammatory Cytokines on Neural Excitability.” \nABSTRACT: Maintaining normal excitability is a key function of our nervous system which is subject to ongoing perturbations such as aging and chronic neurodegeneration. Neuroinflammatory responses which are widely associated with injury and disease are often disregarded as ongoing modulators of brain excitability. Indeed\, neuroinflammatory cytokines such as TNF-α released by resident glial cells in the nervous system can modify ionic conductivity in neurons at nano-molar concentrations at acute and chronic timescales and in turn can mediate emergence of neural dysfunctions observed during disease development. This suggests that understanding how and when cytokines act on neurons could represent targets for therapeutic modulation. Therefore\, we set out to examine in existing literature how strong are the evidence for neuroinflammatory modulation of neural excitability. Surprisingly\, neither the database search using popular bioinformatics tools such as the STRING\, nor the top hits on Pubmed search using keywords such as “cytokine” AND “ion channels” revealed strong evidence for molecular interactions between inflammatory cytokines in the brain and voltage-gated ion channel proteins responsible for neural signaling. However\, a more detailed examination of the literature uncovered a few yet convincing mechanistic studies demonstrating that cytokines can induce changes in ionic conductivity\, ion channel protein expression as well as action potential frequencies. Driven by these findings\, we set out to develop a novel functional interaction score (FIS) to quantitate the strength of evidence for cytokine actions on neural excitability. We then used such scores to generate a protein-protein interactome to enable further application of graph theory-based approaches to analyze the functional links between neuroinflammation and neural excitability. Our analysis and novel scoring also revealed 1-to-N associations between cytokines and ion channel proteins. In my talk\, I will discuss this journey and also share our ongoing innovative approach using the cytokine-ion channel associations in dynamic neuron models as predictive tools to test integrative actions of cytokines on neuronal excitability.
URL:https://qcb.ucla.edu/event/qcbio-research-seminar-jakob-von-morgenland-venugopal/
LOCATION:ZOOM\, CA\, United States
CATEGORIES:Research Seminars
ATTACH;FMTTYPE=image/jpeg:https://wp-misc.lifesci.ucla.edu/qcb/wp-content/uploads/sites/14/2021/05/Jakob-von-Morgenland.jpg
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