Institute for Quantitative and Computational Biosciences

Frontiers in Computational Biosciences Seminar Series: Seth Bordenstein, PhD, Director, One Health Microbiome Center, Huck Endowed Chair in Microbiome Sciences, The Pennsylvania State University
2023-10-23 12:00 - 13:00 (America/Los_Angeles) | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “human microbiome variation across ethnicity and race”
Hosted by Nandita Garud for Genetics & Genomics

QCBio Research Seminar: Andras Gyorgy, Assistant Professor of Electrical Engineering and Bioengineering - NYU Abu Dhabi
2023-07-24 11:00 - 12:00 | Boyer Hall 130
TITLE: “Inducible plasmid copy number control and a blueprint for a synthetic genetic feedback optimizer”
ABSTRACT: The ability to control gene expression has been paradigm shifting for all areas of biological research, especially for synthetic biology. This talk will focus on two recent advancements in gene expression control. First, TULIP (TUnable Ligand Inducible Plasmid) is presented: a self-contained plasmid with inducible copy number control, designed for portability across various Escherichia coli strains commonly used for cloning, protein expression, and metabolic engineering. As demonstrated through multiple application examples, flexible plasmid copy number control via TULIP accelerates the design and optimization of gene circuits, enables efficient probing of metabolic burden, and facilitates the prototyping and recycling of modules in different genetic contexts. Second, the blueprint of a genetic feedback module is presented to optimize a broadly defined performance metric by adjusting the production and decay rate of a set of regulator species. The optimizer can be implemented by combining available synthetic biology parts and components, and it can be readily integrated with existing pathways and genetically encoded biosensors to ensure its successful deployment in a variety of settings when relying on mass action kinetics-based dynamics and parameter values typical in Escherichia coli.

BIG Summer Research Seminar: Jimmy Hu, Assistant Professor in the Division of Oral Biology & Medicine at the UCLA School of Dentistry
2023-07-21 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Building a tooth from transcriptome to tissue morphogenesis”
ABSTRACT: During craniofacial development, the oral epithelium begins as a morphologically homogeneous tissue that gives rise to locally complex structures, including the teeth, salivary glands, and taste buds. How the epithelium is initially patterned and later shaped to generate diverse organ and cell types remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we mapped the transcriptional landscape of embryonic day (E) 12 mouse mandibular epithelia at single cell resolution. Our analysis identified key transcription factors and gene regulatory networks that define different epithelial cell types. By examining the spatiotemporal patterning process along the oral-aboral axis, our results inform a model where the dental field is progressively confined to its position by the formation of the aboral epithelium anteriorly and the non-dental oral epithelium posteriorly. As dental suprabasal cells are enriched with genes related to actomyosin-based motility, we next studied mutant embryos lacking non-muscle myosin II to explore the roles of cellular forces during tooth morphogenesis. We found that myosin II is critical for maintaining cell-cell adhesion and for efficient cellular movement that drives dental epithelial invagination. Together, our results describe the transcriptional regulation during oral epithelial patterning and unveil an actomyosin-based mechanism that promotes tooth invagination.

BIG Summer Research Seminar: Xianghong Jasmine Zhou, Professor, Pathology and Laboratory Medicine at UCLA
2023-07-14 16:00 - 17:00 | Boyer Hall 159
TITLE: “Liquid Biopsies for Precision Oncology.”
ABSTRACT: Liquid biopsies are new diagnostic approaches to profile molecular features of solid tumors by blood, saliva, urine, and other body fluids. Such approaches offer non-invasive options in early cancer detection, tumor sampling, continuous monitoring, and designing personalized therapeutic options. Therefore, liquid biopsies have the potential to transform the field of clinical oncology. Recently, cell-free DNA analysis from a simple blood draw received enormous attention for its promise in these applications. In this talk, we will discuss several novel computational and experimental technologies on using cell-free DNA for the detection and monitoring of cancer and other diseases.

BIG Summer Research Seminar: Xia Yang, Professor, Integrative Biology and Physiology Molecular and Medical Pharmacology at UCLA
2023-07-07 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Single Cell Multiomics Integration to Understand Complex Diseases.”
ABSTRACT: Recent advances in single cell multiomics technologies such as single cell RNA-seq, single cell ATAC-seq, and spatial transcriptomics have brought enormous opportunities that enable our understanding of the molecular underpinnings of pathophysiology at a single cell or cell type resolution. However, integrative analysis across single cell multiomics domains has proven challenging. I will introduce our recent efforts in single cell multiomics integration and gene regulatory network modeling, present computational tools to carry out these analyses, and showcase application examples in studies of various complex diseases.

BIG Summer Research Seminar: Eric Deeds, Associate Professor, Integrative Biology & Physiology - Vice Chair, Life Sciences Core at UCLA
2023-06-30 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “A lack of distinct cellular identities in scRNA-seq data: revisiting Waddington’s landscape.”
ABSTRACT: Single-cell RNA sequencing is revolutionizing our understanding of development, differentiation and disease. Analysis of this data is often challenging, however, and tasks like clustering cells to uncover distinct cellular identities sometimes yields results that fail to align with existing biological knowledge. We analyzed publicly available data where the cell identity for each cell is known a priori, and found that cells of very different types and lineages do not occupy distinct regions of gene expression space. Rather, cells from different lineages overlap extensively with one another, significantly complicating attempts to recover distinct identities within the data. Indeed, our analysis of available epigenetic data for a wide variety of tissues and organisms revealed these data are not consistent with the predictions of Waddington’s landscape, suggesting a need to revisit our picture of gene expression changes during differentiation and development.

BIG Summer Research Seminar: Brunilda Balliu, Assistant Professor in the Departments of Pathology & Laboratory Medicine and Computational Medicine at UCLA
2023-06-23 16:30 - 17:00 | ZOOM, CA, United States
TITLE: “FastGxC: a statistical framework for mapping context-specific regulatory variants using bulk and single-cell RNA-seq data.”
ABSTRACT: Recent studies suggest that context-specific eQTLs underlie genetic risk factors for complex diseases. However, methods for identifying them are still nascent, limiting their comprehensive characterization and downstream interpretation of disease-associated variants. In this talk, I will introduce FastGxC, a method to efficiently and powerfully map context-specific eQTLs by leveraging the correlation structure of bulk multi-tissue and single-cell RNA-seq studies. We applied FastGxC to simulated and real bulk and single-cell RNA-Seq data sets and show that FastGxC is orders of magnitude more powerful and computationally efficient than existing eQTL mapping approaches, making previously yearlong computations possible in minutes. In addition, FastGxC provides a three-fold increase in precision to identify relevant tissues and cell types for GWAS variants than standard eQTL mapping approaches.

https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/06/Brunilda-Balliu-62323.mp4

Webinar: Digital Immune Twins: The Future of Healthcare?
2023-05-17 17:30 - 18:30 | Webinar

QCBio Special Virtual Event: "Digital Immune Twins: The Future of Healthcare?"
2023-05-17 17:30 - 18:30 | ZOOM, CA, United States
Join us for an illuminating conversation with:
Alexander Hoffmann, Director, Institute for Quantitative & Computational Biosciences, Thomas M. Asher Professor of Microbiology, UCLA Microbiology, Immunology & Molecular Genetics
Elaine F. Reed, Daljit S. and Elaine Sarkaria Endowed Chair in Diagnostic Medicine, Professor, Pathology and Laboratory Medicine, Director, UCLA Immunogenetics Center
Aaron Meyer, Assistant Professor, Bioengineering
With introductory remarks by
Tracy Johnson, Keith and Cecilia Terasaki Presidential Endowed Chair, Professor, Molecular, Cell & Developmental Biology, Dean of Life Sciences, UCLA College

W23: Advanced Cytoscape
2023-04-25 13:30 - 2023-04-27 16:30 | ZOOM, CA, United States
The workshop will cover experimental approaches to protein interaction determination; processing and presentation of interaction data available from online resources, and the role of interaction data in the interpretation of large scale datasets. Highly encourage: Students should working knowledge of python scripting.

Academic Jobs - Postdoc Career Development Series
2023-04-11 12:00 - 13:00 | ZOOM, CA, United States

QCBio Research Seminar: Nicholas Wang (Boutros), Grad Student, Bioinformatics
2023-03-24 12:30 - 13:00 | ZOOM, CA, United States
TITLE: “Germline structural variants shape prostate cancer clinical and molecular evolution.”
ABSTRACT: Inherited genetic variation profoundly influences cancer risk and outcome. While the impact of germline single nucleotide polymorphisms has been well-studied in several cancer types, the effects of germline structural variants (gSVs) on cancer biology and clinical outcomes is largely unknown. From our cohort of 300 men with localized, intermediate risk prostate cancer, we identified 6,003 gSVs present in at least 3% of patients, with 48 associated with recurrent somatic alterations or clinical outcome. Of these, ~50% associated with expression of nearby genes or intersected with exons or regulatory regions. Using external cohorts, we validated three gSVs that were strongly associated with poor clinical outcomes, including an inversion at chr14q24.1 present in ~20% of patients. Notably, a strong synergistic effect on outcome was observed in patients with somatic TP53 alterations or high genomic instability, defining a new aggressive prostate cancer subtype with chr14INV as a novel, recurrent biomarker.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Nicholas-Wang-32423.mp4

QCBio Research Seminar: Dongyuan Song (Li JJ), Grad Student, Bioinformatics IDP
2023-03-24 12:00 - 12:30 | ZOOM, CA, United States
TITLE: “ClusterDE: a post-clustering differentially expressed (DE) gene identification method robust to false-positive inflation caused by double-dipping”
ABSTRACT: In typical single-cell RNA-seq data analysis, first, a clustering algorithm is applied to cluster cells; then, a statistical method is used to identify the differentially expressed (DE) genes between the cell clusters. However, this common procedure uses the same data twice, an issue known as “double dipping”: the same gene expression data are used to define cell clusters and DE genes, leading to false-positive DE genes even when the cell clusters are spurious. To overcome this challenge, we propose ClusterDE, a post-clustering DE method for controlling the false discovery rate (FDR) regardless of clustering quality. The core idea of ClusterDE is to generate in silico negative control data with only one cluster, which can be used in contrast to real data for evaluating the whole clustering+DE procedure. Using comprehensive simulation and real data analysis, we show that ClusterDE can not only has solid FDR control but also finds cell-type marker genes that are biologically meaningful. ClusterDE is fast, transparent, and adaptive to a wide range of clustering methods and statistical tests.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Dongyuan-Song-32423.mp4

QCBio Research Seminar: Helena Winata (Boutros), Grad Student, Bioinformatics IDP
2023-03-17 12:30 - 13:00 | ZOOM, CA, United States
TITLE: “Efficient, Multi Sample Inference of Cancer Phylogeny.”
ABSTRACT: Cancer is characterized by the ongoing accumulation of somatic mutations that may lead to dysregulated cellular proliferation. The selection of advantageous mutations leads to clonal expansions of progressively more aberrant and fit cancer cells. Reconstructing the evolutionary history of a tumor allows us to understand key events in disease progression and mechanisms that lead to disease lethality. Sequencing multiple tumor samples provide an opportunity to study tumor evolution in much greater detail and accuracy than was previously feasible through single-sample datasets. However, current reconstruction methods utilize stochastic-search algorithms, which iterates through a parameter space to jointly infer clone populations and their phylogeny. As tumor phylogenetic topology increases in complexity, the parameter space grows exponentially, and stochastic-search algorithms become computationally intractable. To circumvent current computational limitations, we developed a heuristic-based algorithm for subclonal reconstruction that leverages fundamental principles of cancer biology to encode heuristics that reduce the solution space to biologically plausible phylogenies. Benchmarking on real and simulated datasets are ongoing, and preliminary results indicate a ten-fold reduction in runtime. We have thus presented a novel method for rapid and optimized reconstruction of tumor evolutionary histories from multi-sample datasets.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Helena-Winata-31723.mp4

QCBio Research Seminar: Jessica Ding (Yang), Grad Student, Molecular, Cellular, and Integrative Physiology
2023-03-17 12:00 - 12:30 | ZOOM, CA, United States
TITLE: “Multi-tissue single-cell level understanding of Alzheimer’s disease points to the therapeutic potential of nutritional and metabolic modulation.”
ABSTRACT: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by extracellular amyloid plaque deposition and intracellular neurofibrillary tangles. The direct cause of abnormal protein accumulation and aggregation is largely unknown, and no treatments exist to effectively delay or prevent development of AD. AD onset and progression is affected by many genetic and environmental factors, and exploration of significant risk factors for AD may help elucidate its complexity. AD is often comorbid with metabolic syndrome, which includes hypertension, elevated blood glucose and triglycerides, and abdominal obesity. We investigate the potential connection between AD and metabolic syndrome by testing the effect of high fructose consumption, omega-3 fatty acid docosahexaenoic acid (DHA), and nicotinamide riboside (NR) on hippocampal and hypothalamic single cell transcriptomes of the 5XFAD mouse model of amyloid accumulation. We report that metabolically challenging 5XFAD mice with fructose promotes expression of certain proinflammatory genes that may further exacerbate neuronal loss. Supplementation of 5XFAD with DHA and NR was shown to downregulate microglial activation genes, but DHA and NR on 5XFAD with fructose background also enhanced specific aspects of microglial function while downregulating fructose-induced exacerbation of proinflammatory genes, which may indicate mechanisms to counteract further worsening of AD by fructose. Overlaying differentially expressed genes (DEGs) onto a microglial gene regulatory network showed fructose, DHA, and NR target shared and specific aspects of the disease subnetwork. We also observed that fructose led to a depletion of an intermediate activated microglial state which was enhanced by DHA and NR. Transcriptomic signatures derived from this study showed high enrichment of GWAS signals including cell-type specific nutrition DEGs, regulatory network modules, and microglia trajectory associated genes. Our study has demonstrated that metabolic modulation impacts AD transcriptomic signatures and has significant implications for the treatment of AD with DHA and NR or modulators that enhance associated mechanisms.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Jessica-Ding-3.17.23.mp4

QCBio/Bioinformatics/Human Genetics seminar: Min Xu, PhD, Assistant Professor, Computational Biology Department, Co-Director, MS in Computational Biology Program, Carnegie Mellon University
2023-03-13 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Automatic analysis of cryo-electron tomography using computer vision and machine learning.”

QCBio Research Seminar: Brandon Tsai (Boutros), Grad Student, Human Genetics
2023-03-10 12:30 - 13:00 | ZOOM, CA, United States
TITLE: “Exercise and tumor genomic landscapes in 2,702 patients with cancer”
ABSTRACT: Approximately two-thirds of cancer diagnoses globally are attributed to modifiable lifestyle factors such as smoking, diet and inactivity. Conversely, regular exercise is linked to decreased risk of multiple cancers. However, the underlying molecular mechanisms are not fully elucidated. Specifically, how exercise impacts tumor genomic landscapes has not been considered. To address this gap, we integrated clinical annotation of exercise exposure with tumor mutational profiling of 2,702 patients with cancer. Exercise exposure was evaluated by validated questionnaire and tumor genomic profiling of ≥ 505 commonly mutated cancer genes was performed using the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actional Cancer Targets (MSK-IMPACT) assay. Among the most represented cancer types were breast (n = 629), lung (n = 525), endometrial (n = 260), colorectal (n = 213) and prostate (n = 177). We found that exercise influences the genomic landscapes of tumors in a cancer-type specific manner. For instance, breast and lung cancers from exercising patients had lower tumor mutation burden (TMB) compared with non-exercisers. A pan-cancer analysis revealed a higher risk ratio among exercisers for mutations in ERBB2 and lower risk ratio for mutations in PIK3CA and CDKN2A. Overall, this study shows that exercise regulates tumor genomic landscapes in a cancer-site specific manner.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Brandon-Tsai-31023.mp4

QCBio Research Seminar: Daniel Ha (Yang), Postdoc, Dept. Integrative Biology and Physiology
2023-03-10 12:00 - 12:30 | ZOOM, CA, United States
TITLE: ““Cross-tissue multiomics studies reveal gutbrain interactions mediating the effect of Akkermansia muciniphila in counteracting fructose-induced obesity”
ABSTRACT: The gut bacterium Akkermansia muciniphila (A. muciniphila) has been implicated in anti-obesity effects, but a systems level understanding of the molecular mechanisms is lacking. We carried out multiomics studies to investigate the molecular cascades mediating the anti-obesity effect of A. muciniphila in a fructoseinduced obesity mouse model. We found that A. muciniphila colonization triggered significant shifts in gut microbiota composition, gut and plasma metabolites, and gene expression in hypothalamic neurons. Multiomics integration and network analysis prioritized the metabolite oleoylethanolamide (OEA) in the gut and circulation as a regulator of gut-brain interactions that underlie the A. muciniphila antiobesity effect. Oral administration of OEA counteracted the fructose-induced obesity through the regulation of hypothalamic anorexigenic neuropeptides such as oxytocin and arginine vasopressin. Our multiomics investigation and experimental validation elucidates the molecular regulators and pathways involved in the communication between A. muciniphila in the gut and hypothalamic neurons that counter fructose-induced obesity.
https://qcb.ucla.edu/wp-content/uploads/sites/14/2023/03/Daniel-Ha-3.10.23.mp4

QCBio/Bioinformatics/Human Genetics seminar: Zoltán Kutalik, PhD, Associate Professor, University of Lausanne
2023-03-06 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Pushing the boundaries of causal inference.”

QCBio Research Seminar: Gregoire Altan-Bonnet, Principal Investigator – Immunodynamics group Laboratory of Integrative Cancer Immunology NCI, NIH, Bethesda MD
2023-03-06 14:00 - 15:00 | Boyer 159
TITLE: “Stochasticity in cancer immunotherapies: identifying the T cell subset that sparks tumor eradication”
ABSTRACT: We use an ex vivo model of tumor eradication to dissect the fundamental variability of clinical outcomes in cancer immunotherapies. We demonstrate that there exists an inherent stochastic variability in immune responses, based on the low abundance of hyper-responsive naïve T cells (so-called Spark T cells) and feedback regulations amongst leukocytes. We introduce a methodology (combining hierarchical clustering of single-cell measurements and statistical matching with functional outcomes) to identify Spark T cells. We then carry out functional tests to model the mechanics of Spark T cells igniting global immune responses and tumor rejection.

QCBio/Center for Biological Physics: Gregoire Altan-Bonnet, Principal Investigator – Immunodynamics group Laboratory of Integrative Cancer Immunology NCI, NIH, Bethesda MD
2023-03-03 16:00 - 17:00 | Boyer Hall 130

Webinar: Mapping The Brain With 100 Billion Cells, Is This an Impossible Task?
2023-03-01 17:30 - 18:30 | ZOOM, CA, United States

QCBio Webinar: Mapping The Brain With 100 Billion Cells, Is This an Impossible Task?
2023-03-01 17:30 - 18:30 | ZOOM, CA, United States
A conversation featuring:
Roy Wollman, Ph.D.
Professor, UCLA Integrative Biology & Physiology and Chemistry & Biochemistry
Jingyi Jessica Li, Ph.D.
Professor, UCLA Statistics, Biostatistics, Computational Medicine and Human Genetics
Hong-Wei Dong, Ph.D.
Professor, UCLA Neurobiology – Director, UCLA Brain Research & Artificial Intelligence Nexus (B.R.A.I.N.)
Introduction by:
Alexander Hoffmann, Ph.D.
Director, Institute for Quantitative & Computational Biosciences – Thomas M. Asher Professor of Microbiology, UCLA Microbiology, Immunology & Molecular Genetics

QCBio/Bioinformatics/Human Genetics seminar: Molly Przeworski, PhD, Professor, Biological Sciences, Systems Biology, Columbia University
2023-02-27 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Why do human germline mutation rates depend on sex and age.”

QCBio/Bioinformatics/Human Genetics seminar: Jonathan Sebat, PhD, Chief, Beyster Center for Molecular Genomics of Neuropsychiatric Diseases, Professor of Psychiatry and Cellular and Molecular Medicine, UC San Diego
2023-02-13 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “TBA”

QCBio/Bioinformatics/Human Genetics seminar: Haiyuan Yu, PhD, Professor, Biological Statistics and Computational Biology, Cornell University
2023-02-06 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “New perspectives to dissect global dynamics of protein interactome and gene regulation in disease.”

QCBio/Bioinformatics/Human Genetics seminar: Soojin Yi, PhD, Professor, Ecology, Evolution, and Marine Biology, UC Santa Barbara
2023-01-30 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “DNA Methylation in Brain Evolution and Neuropsychiatric Disorders.”

QCBio/Bioinformatics/Human Genetics seminar: Pleuni Pennings, PhD, Associate Professor, Biology, San Francisco State University
2023-01-23 16:00 - 17:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Part 1: “How important is evolution vs transmission of drug resistance”.
Part 2: “Computing skills for every biology student.”

QCBio Research Seminar: Friedrich Simmel, Department of Bioscience, School of Natural Sciences, TU Munich, Germany
2023-01-13 14:00 - 15:00 | Boyer 159, 611 Charles E. Young Dr. E., Los Angeles, CA, 90095, United States
TITLE: “Electric actuation of DNA-based molecular machines.”
ABSTRACT: A wide range of machine-like molecular assemblies have been generated over the past years. Most of them have been driven (or controlled) by DNA hybridization, utilization of buffer changes, or using chemical modifications such as photoswitches. A more recently explored strategy is the use of electrical fields for the manipulation of DNA devices, which enables fast and computer-controlled actuation. In the talk, several examples of such DNA origami-based „nanorobotic“ systems will be discussed, including a DNA „robot arm“, molecular springs, an origami based Brownian ratchet with rotary movement, and others. On a slightly different topic, also a novel strategy to control microswimmers using AC electrical fields will be presented.

QCBio/Bioinformatics/Human Genetics seminar: Shamil Sunyaev, PhD, Professor, Biomedical Informatics, Harvard Medical School
2023-01-09 16:00 - 17:00 | Boyer 159
TITLE: “Statistics, Biology and Applications of Human Mutation.”
