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X-WR-CALNAME:Institute for Quantitative and Computational Biosciences
X-ORIGINAL-URL:https://qcb.ucla.edu
X-WR-CALDESC:Events for Institute for Quantitative and Computational Biosciences
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BEGIN:VEVENT
DTSTART;TZID=America/Los_Angeles:20231108T130000
DTEND;TZID=America/Los_Angeles:20231108T133000
DTSTAMP:20231108T223740Z
CREATED:20231102T151931Z
LAST-MODIFIED:20231108T223740Z
UID:25982-1699448400-1699450200@qcb.ucla.edu
SUMMARY:Research-in-Progress (RIP) Seminar: Jonatan Hervoso (Xiao)\, Graduate Student in Bioinformatics
DESCRIPTION:TITLE: “Splicing-specific transcriptome-wide association uncovers novel genetic mechanisms for Schizophrenia.” \nABSTRACT: Recent studies have highlighted the essential role of RNA splicing\, a key mechanism of alternative RNA processing\, in establishing connections between genetic variations and disease. Genetic loci influencing RNA splicing variations show considerable influence on complex traits\, possibly surpassing those affecting total gene expression. Dysregulated RNA splicing has emerged as a major potential contributor to neurological and psychiatric disorders\, likely due to the exceptionally high prevalence of alternatively spliced genes in the human brain. Nevertheless\, establishing direct associations between genetically altered splicing and complex traits has remained an enduring challenge. We introduce Spliced-Transcriptome-Wide Associations (SpliTWAS) to integrate alternative splicing information with GWAS to pinpoint genes linked to traits through exon splicing events. We applied SpliTWAS to two schizophrenia (SCZ) RNA-seq datasets\, BrainGVEX and CommonMind (CMC)\, revealing 137 and 88 trait-associated exons (in 84 and 67 genes)\, respectively.  Enriched biological functions in the associated gene sets converged on neuronal function and development\, immune cell activation\, cellular transport\, which are highly relevant to SCZ. SpliTWAS variants impacted RNA-binding protein (RBP) binding sites\, revealing potential disruption of RNA-protein interactions affecting splicing. We extended the probabilistic fine-mapping method FOCUS to the exon level\, identifying putative causal 36 genes and 48 exons for SCZ. We highlight VPS45 and APOPT1\, where splicing of specific exons was associated with disease risk\, eluding detection by conventional gene expression analysis. Collectively\, this study supports the substantial role of alternative splicing in shaping the genetic basis of SCZ\, providing a valuable approach for future investigations in this area. \n\nhttps://wp-misc.lifesci.ucla.edu/qcb/wp-content/uploads/sites/14/2023/11/Jonatan-Hervoso.mp4
URL:https://qcb.ucla.edu/event/research-in-progress-rip-seminar-jonatan-hervoso-xiao-graduate-student-in-bioinformatics/
LOCATION:ZOOM\, CA\, United States
CATEGORIES:QCBio Seminar Series
ATTACH;FMTTYPE=image/png:https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/11/Hervoso.png
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DTSTART;TZID=America/Los_Angeles:20231108T133000
DTEND;TZID=America/Los_Angeles:20231108T140000
DTSTAMP:20231102T152047Z
CREATED:20231018T092214Z
LAST-MODIFIED:20231102T152047Z
UID:25889-1699450200-1699452000@qcb.ucla.edu
SUMMARY:Research-in-Progress (RIP) Seminar: Xiaolu Guo (Hoffmann)\, Postdoc in Microbiology\, Immunology & Molecular Genetics
DESCRIPTION:TITLE: “Modeling the heterogenous NFκB dynamics of single immune cells.” \nABSTRACT: Macrophages function as immune sentinel cells\, initiating appropriate and specialized immune responses to a great variety of pathogens.  The transcription factor NFκB controls macrophage gene expression responses\, and its temporal dynamics enable stimulus-specificity of these responses.  Using a fluorescent reporter mouse our laboratory recently generated large amounts of single-cell NFκB dynamic data and identified dynamic features\, termed ‘signaling codons’\, that convey information to the nucleus about stimulus identity and dose.  Here\, we aimed to recapitulate the stimulus-specific but highly cell-to-cell heterogeneous NFκB dynamics with a mathematical model of the signaling network.  The parameters that are subject to biological variation provide the potential to account for the heterogeneity in observed stimulus responses.  We estimated parameter distributions using the Stochastic Approximation Expectation Maximization (SAEM) approach and then fit the individual cell data using Bayesian maximum a posteriori (MAP) estimation.  Visual inspection revealed an excellent fit with the data.  To quantitatively evaluate the fitting performance\, we compared the experimental and predicted distributions of NFκB signaling codons.  Further\, we identified biochemical reactions that may account for the cellular heterogeneity in NFκB dynamics.  We verified that the stimulus-specificity of the virtual macrophage NFκB responses was consistent with their live-cell counterparts\, as assessed by mutual information and machine learning classification. Additionally\, the mathematical model allowed us extend experimental dose response studies\, revealing the doses that maximize information. Furthermore\, the virtual NFκB macrophages enabled the exploration of individual cell responses to different ligands. Leveraging this capability\, we made predictions regarding combinatorial ligands\, that were then experimentally tested. Discrepancies between the experimental results and model predictions led to the identification of a competition mechanism between CpG and PolyIC for endosome trafficking\, resulting in non-integrative responses behavior. Our results establish a mathematical modeling tool that may be used to study the molecular determinants of response specificity and dynamical coding in immune sentinel cells at the single cell level.
URL:https://qcb.ucla.edu/event/research-in-progress-rip-seminar-xiaolu-guo-hoffmann-postdoc-in-microbiology-immunology-molecular-genetics/
LOCATION:ZOOM\, CA\, United States
CATEGORIES:QCBio Seminar Series
ATTACH;FMTTYPE=image/png:https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/10/Xiaolu.png
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BEGIN:VEVENT
DTSTART;TZID=America/Los_Angeles:20231108T160000
DTEND;TZID=America/Los_Angeles:20231108T170000
DTSTAMP:20231024T101808Z
CREATED:20231024T101808Z
LAST-MODIFIED:20231024T101808Z
UID:25927-1699459200-1699462800@qcb.ucla.edu
SUMMARY:Special Seminar: Sara Monaco\, Managing Editor\, European Molecular Biology Organization (EMBO)
DESCRIPTION:TITLE: “The new culture of preprint peer-review”
URL:https://qcb.ucla.edu/event/special-seminar-sara-monaco-managing-editor-european-molecular-biology-organization-embo/
LOCATION:Boyer Hall 130
CATEGORIES:QCBio Seminar Series
ATTACH;FMTTYPE=image/jpeg:https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/10/Sara-Monico.jpg
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