Forthcoming events in this series

Fri, 17 Jun 2022

14:00 - 15:00
L6

### Data-driven early detection of potential high risk SARS-CoV-2 variants

Dr Marcin J. Skwark
Abstract

Recent advances in Deep Learning have enabled us to explore new application domains in molecular biology and drug discovery - including those driven by complex processes that defy analytical modelling.  However, despite the combined forces of increased data, improving compute resources and continuous algorithmic innovation all bringing previously intractable problems into the realm of possibility, many advances are yet to make a tangible impact for life science discovery.  In this talk, Dr Marcin J. Skwark will discuss the challenge of bringing machine learning innovation to tangible real-world impact.  Following a general introduction of the topic, as well as newly available methods and data, he will focus on the modelling of COVID-19 variants and, in particular, the DeepChain Early Warning System (EWS) developed by InstaDeep in collaboration with BioNTech.  With thousands of new, possibly dangerous, SARS-CoV-2 variants emerging each month worldwide, it is beyond humanities combined capacity to experimentally determine the immune evasion and transmissibility characteristics of every one.  EWS builds on an experimentally tested AI-first computational biology platform to evaluate new variants in minutes, and is capable of risk monitoring variant lineages in near real-time.  This is done by combining an AI-driven protein structure prediction framework with large, spike protein sequence-oriented Transformer models to allow for rapid simulation-free assessment of the immune escape risk and expected fitness of new variants, conditioned on the current state of the world.  The system has been extensively validated in cooperation with BioNTech, both in terms of host cell infection propensity (including experimental assays of receptor binding affinity), and immune escape (pVNT assays with monoclonal antibodies and real-life donor sera). In these assessments, purely unsupervised, data-first methods of EWS have shown remarkable accuracy. EWS flags and ranks all but one of the SARS-CoV-2 Variants of Concern (Alpha, Beta, Gamma, Delta… Omicron), discriminates between subvariants (e.g. BA.1/BA.2/BA.4 etc. distinction) and for most of the adverse events allows for proactive response on the day of the observation. This allows for appropriate response on average six weeks before it is possible for domain experts using domain knowledge and epidemiological data. The performance of the system, according to internal benchmarks, improves with time, allowing for example for supporting the decisions on the emerging Omicron subvariants on the first days of their occurrence. EWS impact has been notable in general media [2, 3] for the system's applicability to a novel problem, ability to derive generalizable conclusions from unevenly distributed, sparse and noisy data, to deliver insights which otherwise necessitate long and costly experimental assays.

Fri, 10 Jun 2022

14:00 - 15:00
L6

### Systems-mechanobiology of health and disease

Dr Fabian Spill
(School of Mathematics University of Birmingham)
Abstract

Experimental biologists study diseases mostly through their abnormal molecular or cellular features. For example, they investigate genetic abnormalities in cancer, hormonal imbalances in diabetes, or an aberrant immune system in vascular diseases. Moreover, many diseases also have a mechanical component which is critical to their deadliness. Most notably, cancer kills typically through metastasis, where the cancer cells acquire the capability to remodel their adhesions and to migrate. Solid tumours are also characterised by physical changes in the extracellular matrix – the material surrounding the cells. While such physical changes are long known, only relatively recent research revealed that cells can sense altered physical properties and transduce them into chemical information. An example is the YAP/TAZ signalling pathway that can activate in response to altered matrix mechanics and that can drive tumour phenotypes such as the rate of cell proliferation.
Systems-biology models aim to study diseases holistically. In this talk, I will argue that physical signatures are a critical part of many diseases and therefore, need to be incorporated into systems-biology. Crucially, physical disease signatures bi-directionally interact with molecular and cellular signatures, presenting a major challenge to developing such models. I will present several examples of recent and ongoing work aimed at uncovering the relations between mechanical and molecular/cellular signatures in health and disease. I will discuss how blood vessel cells interact mechano-chemically with each other to regulate the passage of cells and nutrients between blood and tissue and how cancer cells grow and die in response to mechanical and geometrical stimuli.

Fri, 03 Jun 2022

14:00 - 15:00

Fri, 27 May 2022

14:00 - 15:00
L6

### Coping with mechanical stress: tissue dynamics in development and repair

Prof Yanlan Mao
(Laboratory for Molecular Cell Biology UCL)
Abstract

During growth and development, tissue dynamics, such as tissue folding, cell intercalations and oriented cell divisions, are critical for shaping tissues and organs. However, less is known about how tissues regulate their dynamics during tissue homeostasis and repair, to maintain their shape after development. In this talk, we will discuss how differential growth rates can generate precise folds in tissues. We will also discuss how tissues respond to mechanical perturbations, such as stretching or wounding, by altering their actomyosin contractile structures, to change tissue dynamics, and thus preserve tissue shape and patterning. We combine genetics, biophysics and computational modelling to study these processes.

Fri, 20 May 2022

14:00 - 15:00
L6

### Causal inference, big data and public health: estimating effectiveness and quantifying waning effectiveness of COVID-19 vaccines

Prof Jonathan Sterne
(Department of Population Health Sciences University of Bristol)
Abstract

Effectiveness of COVID-19 vaccines was first demonstrated in randomised trials, but many questions of vital importance to vaccination policies could only be addressed in subsequent observational studies. The pandemic led to a step change in the availability of population-level linked electronic health record data, analysed in privacy-protecting Trusted Research Environments, across the UK. I will discuss methodological approaches to estimating causal effects of COVID-19 vaccines, and their application in estimating vaccine effectiveness and quantifying waning vaccine effectiveness. I will present results from recent analyses using detailed linked data on up to 24 million people in the OpenSAFELY Trusted Research Environment, which was developed by the University of Oxford's Bennett Institute for Applied Data Science.

Fri, 13 May 2022

14:00 - 15:00
L6

### Integrative analytics connecting genotype and phenotype for precision oncology

Dr Ian Overton
(School of Medicine Dentistry and Biomedical Science Queens University Belfast)
Abstract

Understanding the molecular mechanisms that control the biology of health and disease requires development of models that traverse multiple scales of organisation in order to encapsulate the relationships between genes and linking to observable phenotypes. Measuring, parameterising and simulating the entire system that determines these phenotypes in exhaustive detail is typically impossible due to the underlying biological complexity, our limited knowledge and the paucity of available data. For example, approximately one third of human genes are poorly characterised and most genes perform multiple functions, which manifest according to the surrounding biochemical context. Indeed, new functions continue to emerge even for deeply studied genes. Therefore, simplifying abstractions in concert with empirical analysis of matched genome-scale and descriptive data are valuable strategies to fill knowledge gaps relevant to a focused biomedical question or hypothesis.

Epithelial plasticity is a key driver of cancer progression and is associated with the most life-threatening phenotypes; specifically, metastasis and drug resistance. Computational methods developed in my group enable modelling the molecular control of important cancer phenotypesWe applied a machine learning approach for genome-wide context-specific biochemical interaction network inference (CoSNI) to map gene function for the Epithelial to Mesenchymal Transition cell programme (EMT_MAP), predicting new mechanisms in control of cancer invasion. Analysis of patient data with EMT_MAP and our NetNC algorithm [Cancers 2020;12:2823; https://github.com/overton-group/NetNC] enabled discovery of candidate renal cancer prognostic markers with clear advantages over standard statistical approaches. NetNC recovers the network-defined signal in noisy data, for example distinguishing functional EMT Transcription Factor targets from ‘neutral’ binding sites and defining biologically coherent modules in renal cancer drug response time course data. These and other approaches, including SynLeGG (Nucleic Acids Research 2021;49:W613-8, www.overton-lab.uk/synleggand an information-theoretic approach to causality (GABIoffer mechanistic insights and opportunity to predict candidate cancer Achilles’ heels for drug discovery. Computational results were validated in follow-up experiments, towards new clinical tools for precision oncology.

Fri, 06 May 2022

14:00 - 15:00
L6

### Intrinsic instability of the dysbiotic microbiome revealed through dynamical systems inference at ecosystem-scale

Dr Travis Gibson
(Harvard Medical School)
Abstract

Dynamical systems models are a powerful tool for analyzing interactions in ecosystems and their intrinsic properties such as stability and resilience. The human intestinal microbiome is a complex ecosystem of hundreds of microbial species, critical to our health, and when in a disrupted state termed dysbiosis, is involved in a variety of diseases.  Although dysbiosis remains incompletely understood, it is not caused by single pathogens, but instead involves broader disruptions to the microbial ecosystem.  Dynamical systems models would thus seem a natural approach for analyzing dysbiosis, but have been hampered by the scale of the human gut microbiome, which constitutes hundreds of thousands of potential ecological interactions, and is profiled using sparse and noisy measurements. Here we introduce a combined experimental and statistical machine learning approach that overcomes these challenges to provide the first comprehensive and predictive model of microbial dynamics at ecosystem-scale. We show that dysbiosis is characterized by competitive cycles of interactions among microbial species, in contrast to the healthy microbiome, which is stabilized by chains of positive interactions initiated by resistant starch-degrading bacteria. To achieve these results, we created cohorts of “humanized” gnotobiotic mice via fecal transplantation from healthy and dysbiotic human donors, and subjected mice to dietary and antibiotic perturbations, in the densest temporal interventional study to date. We demonstrate that our probabilistic machine learning method achieves scalability while maintaining interpretability on these data, by inferring a small number of modules of bacterial taxa that share common interactions and responses to perturbations. Our findings provide new insights into the mechanisms of microbial dysbiosis, have potential implications for therapies to restore the microbiome to treat disease, and moreover offer a powerful framework for analyzing other complex ecosystems.

Fri, 29 Apr 2022

14:00 - 15:00
Virtual

### Spreading mechanics and differentiation of astrocytes during retinal development

Prof Tracy Stepien
(Department of Mathematics University of Florida)
Abstract

In embryonic development, formation of the retinal vasculature is  critically dependent on prior establishment of a mesh of astrocytes.
Astrocytes emerge from the optic nerve head and then migrate over the retinal surface in a radially symmetric manner and mature through
differentiation.  We develop a PDE model describing the migration and  differentiation of astrocytes, and numerical simulations are compared to
experimental data to assist in elucidating the mechanisms responsible for the distribution of astrocytes via parameter analysis. This is joint
work with Timothy Secomb.

Fri, 11 Mar 2022

14:00 - 15:00
L3

### Examples of artificial intelligence uses in target identification and drug discovery

Dr Ramneek Gupta
(Novo Nordisk Research Centre Oxford University of Oxford)
Abstract

As biological data has become more accessible and available in biology and healthcare, we find increasing opportunities to leverage artificial intelligence to help with data integration and picking out patterns in complex data. In this short talk, we will provide glimpses of what we do at the Novo Nordisk Research Centre Oxford towards understanding patient journeys, and in the use of knowledge graphs to draw insights from diverse biomedical data streams

Fri, 04 Mar 2022

14:00 - 15:00
L3

### Do we understand Fibonacci numbers in plants?

Dr Jonathan Swinton
(Swinton.net)
Abstract

Fibonacci numbers in plants, such as in sunflower spiral counts, have long fascinated mathematicians. For the last thirty years, most analyses have been variants of a Standard Model in which plant organs are treated as point nodes successively placed on a cylinder according to a given function of the previous node positions, not too close or too far away from the existing nodes. These models usually lead to lattice solutions. As a parameter of the model, like the diameter of the cylinder, is changed, the lattice can transition to another, more complex lattice, with a different spiral count. It can typically be proved that these transitions move lattice counts to higher Fibonacci numbers. While mathematically compelling, empirical validation of this Standard Model is as yet weak, even though the underlying molecular mechanisms are increasingly well characterised.

In this talk I'll show a gallery of Fibonacci patterning and give a brief history of mathematical approaches, including a partially successful attempt by Alan Turing. I'll describe how the classification of lattices on cylinders connects both to a representation of $SL(2,Z)$ and to applications through defining the constraint that any model must satisfy to show Fibonacci structure. I'll discuss a range of such models, how they might be used to make testable predictions, and why this matters.

From 2011 to 2017 Jonathan Swinton  was a visiting professor to MPLS in Oxford in Computational Systems Biology. His new textbook Mathematical Phyllotaxis will be published  soon, and his Alan Turing's Manchester will be republished by The History Press in May 2022.

Fri, 25 Feb 2022

14:00 - 15:00
L3

### Navigating through a noisy world

Prof Kevin Painter
(Interuniversity Department of Regional & Urban Studies and Planning Politecnico di Torino)
Abstract

In collective navigation a population travels as a group from an origin to a destination. Famous examples include the migrations of birds and whales, between winter and summer grounds, but collective movements also extend down to microorganisms and cell populations. Collective navigation is believed to improve the efficiency of migration, for example through the presence of more knowledgeable individuals that guide naive members ("leader-follower behaviour") or through the averaging out of individual uncertainty ("many wrongs"). In this talk I will describe both individual and continuous approaches for modelling collective navigation. We investigate the point at which group information becomes beneficial to migration and how it can help a population navigate through areas with poor guidance information. We also explore the effectiveness of different modes through which a leader can herd a group of naïve followers. As an application we will consider the impact of noise pollution on the migration of whales through the North Sea.

Fri, 18 Feb 2022

14:00 - 15:00
L3

### Cells in tissue can communicate long-range via diffusive signals

Prof Jun Allard
(Dept of Mathematics UCI)
Abstract

In addition, another class of cell-cell communication is by long, thin cellular protrusions that are ~100 microns (many cell-lengths) in length and ~100 nanometers (below traditional microscope resolution) in width. These protrusions have been recently discovered in many organisms, including nanotubes humans and airinemes in zebrafish. But, before establishing communication, these protrusions must find their target cell. Here we demonstrate airinemes in zebrafish are consistent with a finite persistent random walk model. We study this model by stochastic simulation, and by numerically solving the survival probability equation using Strang splitting. The probability of contacting the target cell is maximized for a balance between ballistic search (straight) and diffusive (highly curved, random) search. We find that the curvature of airinemes in zebrafish, extracted from live cell microscopy, is approximately the same value as the optimum in the simple persistent random walk model. We also explore the ability of the target cell to infer direction of the airineme’s source, finding the experimentally observed parameters to be at a Pareto optimum balancing directional sensing with contact initiation.

Fri, 11 Feb 2022

14:00 - 15:00
Virtual

### Data science topics related to neurogenomics

Prof Mark Gerstein
(Department of Molecular Biophysics and Biochemistry Yale University)
Abstract

My seminar will discuss various data-science issues related to
neurogenomics. First, I will focus on classic disorders of the brain,
which affect nearly a fifth of the world's population. Robust
phenotype-genotype associations have been established for several
psychiatric diseases (e.g., schizophrenia, bipolar disorder). However,
understanding their molecular causes is still a challenge. To address
this, the PsychENCODE consortium generated thousands of transcriptome
(bulk and single-cell) datasets from 1,866 individuals. Using these
data, we have developed interpretable machine learning approaches for
deciphering functional genomic elements and linkages in the brain and
psychiatric disorders. Specifically, we developed a deep-learning
model embedding the physical regulatory network to predict phenotype
from genotype. Our model uses a conditional Deep Boltzmann Machine
architecture and introduces lateral connectivity at the visible layer
to embed the biological structure learned from the regulatory network
and QTL linkages. Our model improves disease prediction (6X compared
to additive polygenic risk scores), highlights key genes for
disorders, and imputes missing transcriptome information from genotype
data alone. Next, I will look at the "data exhaust" from this activity
- that is, how one can find other things from the genomic analyses
than what is necessarily intended. I will focus on genomic privacy,
which is a main stumbling block in tackling problems in large-scale
neurogenomics. In particular, I will look at how the quantifications
of expression levels can reveal something about the subjects studied
and how one can take steps to sanitize the data and protect patient
anonymity. Finally, another stumbling block in neurogenomics is more
accurately and precisely phenotyping the individuals. I will discuss
some preliminary work we've done in digital phenotyping.

Fri, 04 Feb 2022

14:00 - 15:00
Virtual

### A unifying theory of branching morphogenesis

Prof Ben Simons
(DAMTP University of Cambridge)
Abstract

The morphogenesis of branched tissues has been a subject of long-standing interest and debate. Although much is known about the signaling pathways that control cell fate decisions, it remains unclear how macroscopic features of branched organs, including their size, network topology and spatial patterning, are encoded. Based on large-scale reconstructions of the mouse mammary gland and kidney, we show that statistical features of the developing branched epithelium can be explained quantitatively by a local self-organizing principle based on a branching and annihilating random walk (BARW). In this model, renewing tip-localized progenitors drive a serial process of ductal elongation and stochastic tip bifurcation that terminates when active tips encounter maturing ducts. Finally, based on reconstructions of the developing mouse salivary gland, we propose a generalisation of BARW model in which tips arrested through steric interaction with proximate ducts reactivate their branching programme as constraints become alleviated through the expansion of the underlying matrix. This inflationary branching-arresting random walk model presents a general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the matrix into which it expands.

Fri, 28 Jan 2022

14:00 - 15:00
Virtual

### Multiscaling the CRISPR-cas revolution from gene editing to viral detection

Prof Giulia Palermo
(Department of Bioengineering University of California Riverside)
Abstract

CRISPR is synonymous with a transformative genome editing technology that is innovating basic and applied sciences. I will report about the use of computational approaches to clarify the molecular basis and the gene-editing function of CRISPR-Cas9 and newly discovered CRISPR systems that are emerging as powerful tools for viral detection, including the SARS-CoV-2 coronavirus. We have implemented a multiscale approach, which combines classical molecular dynamics (MD) and enhanced sampling techniques, ab-initio MD, mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approaches and constant pH MD (CpH MD), as well as cryo-EM fitting tools and graph theory derived analysis methods, to reveal the mechanistic basis of nucleic acid binding, catalysis, selectivity, and allostery in CRISPR systems. Using a Gaussian accelerated MD method and the Anton-2 supercluster we determined the conformational activation of CRISPR-Cas9 and the selectivity mechanism against off-target sequences. By applying network models graph theory, we have characterized a mechanism of allosteric regulation, transferring the information of DNA binding to the catalytic sites for cleavages. This mechanism is now being probed in novel Anti-CRISPR proteins, forming multi-mega Dalton complexes with the CRISPR enzymes and used for gene regulation and control. CpH MD simulations have been combined with ab-initio MD and a mixed QM/MM approach to establish the catalytic mechanism of DNA cleavage. Finally, by using multi-microsecond MD simulations we have recently probed a mechanism of DNA-induced of activation in the Cas12a enzyme, which underlies the detection of viral genetic elements, including the SARS-CoV-2 coronavirus. Overall, our outcomes contribute to the mechanistic understanding of CRISPR-based gene-editing technologies, providing information that is critical for the development of improved gene-editing tools for biomedical applications.

Fri, 21 Jan 2022

14:00 - 15:00
L3

### A mechanochemical instability drives vertebrate gastrulation

Prof Mattia Serra
(Department of Physics University of California San Diego)
Abstract

Gastrulation is a critical event in vertebrate morphogenesis, characterized by coordinated large-scale multi-cellular movements. One grand challenge in modern biology is understanding how spatio-temporal morphological structures emerge from cellular processes in a developing organism and vary across vertebrates. We derive a theoretical framework that couples tissue flows, stress-dependent myosin activity, and actomyosin cable orientation. Our model, consisting of a set of nonlinear coupled PDEs, predicts the onset and development of observed experimental patterns of wild-type and perturbations of chick gastrulation as a spontaneous instability of a uniform state. We use analysis and numerics to show how our model recapitulates the phase space of gastrulation morphologies seen across vertebrates, consistent with experiments. Altogether, this suggests that early embryonic self-organization follows from a minimal predictive theory of active mechano-sensitive flows.

Fri, 03 Dec 2021

14:00 - 15:00
L3

### When cardiac imaging meets computational modeling

Dr Vicky Wang
Abstract

Over the past decades, the morbidity and mortality associated with cardiovascular disease have reduced due to advancements in patient care. However, cardiovascular disease remains the world’s leading cause of death, and the prevalence of myocardial pathologies remains significant. Continued advancements in diagnostics and therapeutics are needed to further drive down the social and economic burden of cardiac disease in both developed and developing countries.

Routine clinical evaluation of patients with cardiovascular disease includes non-invasive imaging, such as echocardiography (echo), cardiac magnetic resonance imaging (MRI), and/or CT, and where appropriate, invasive investigation with cardiac catheterisation However, little clinical information is available regarding the linkage between structural and function remodelling of the heart and the intrinsic biomechanical properties of heart muscle which cannot be measured in patients with cardiovascular diseases.

The lack of detailed mechanistic understanding about the change in biomechanical properties of heart muscle may play a significant role in non-specific diagnosis and patient management. Bioengineering approaches, such as computational modelling tools, provide the perfect platform to analyze a wealth of clinical data of individual patients in an objective and consistent manner to augment and enrich existing personalized clinical diagnoses and precise treatment planning by building 3D computational model of the patient's heart.

In my presentation, I will present my research efforts in 1) developing integrative 3D computational modeling platform to enable model-based analysis of medical images of the heart; 2) studying the biomechanical mechanisms underpinning various forms of heart failure using pre-clinica experimental data; 3) applying personalized modeling pipeline to clinical heart failure patient data to non-invasively estimate mechanical properties of the heart muscle on a patient-specific basis; 4) performing in silico simulation of cardiac surgical procedures to evaluate efficacy of mitral clip in treating ischemic mitral regurgitation.

My presentation aims to showcase the power of combining computational modeling and bioengineering technologies with medical imaging to enrich and enhance precision and personalized medicine.

Fri, 26 Nov 2021

14:00 - 15:00
L3

### New insights into cancer metastasis and evolution from combined experimental, clinical, and modelling analysis

Dr Erik Sahai
(The Francis Crick Institute London)
Fri, 19 Nov 2021

14:00 - 15:00
L3

### Predicting atrial fbrillation treatment outcomes through mathematical modelling, signal processing and machine learning

Dr Caroline Roney
(Kings’ College London)
Abstract

Catheter ablation and antiarrhythmic drug therapy approaches for treatment of atrial fibrillation are sub-optimal. This is in part because it is challenging to predict long-term response to therapy from short-term measurements, which makes it difficult to select optimal patient-specific treatment approaches. Clinical trials identify patient demographics that provide prediction of long-term response to standard treatments across populations. Patient-specific biophysical models can be used to assess novel treatment approaches but are typically applied in small cohorts to investigate the acute response to therapies. Our overall aim is to use machine learning approaches together with patient-specific biophysical simulations to predict long-term atrial fibrillation recurrence after ablation or drug therapy in large populations.

In this talk I will present our methodology for constructing personalised atrial models from patient imaging and electrical data; present results from biophysical simulations of ablation treatment; and finally explain how we are combining these methodologies with machine learning techniques for predicting long-term treatment outcomes.

Fri, 12 Nov 2021

14:00 - 15:00
L3

### Tools and approaches to build and analyze multiscale computational models in biology -TB as a case study

Prof Denise Kirschner
(Department of Microbiology and Immunology University of Michigan Medical Schoo)
Abstract

In this talk, I will give an overview of our multi-scale models that we have developed to study a number of aspects of the immune response to infection.  Scales that we explore range from molecular to the whole-host scale.  We are also able to study virtual populations and perform simulated clinical trials. We apply these approaches to study Tuberculosis, the disease caused by inhalation of the bacteria, Mycobacterium tuberculosis. It has infected 2 billion people in the world today, and kills 1-2 million people each year, even more than COVID-19. Our goal is to aid in understanding infection dynamics, treatment and vaccines to improve outcomes for this global health burden. I will discuss our frameworks for multi-scale modeling, and the analysis tools and statistical approaches that we have honed to better understand different outcomes at different scales.

Fri, 05 Nov 2021

14:00 - 15:00
L3

### Ensuring chemical safety using maths not rats

Dr Andrew Worth
(Directorate General Joint Research Centre European Commission)
Abstract

This presentation will focus on the role of mathematical modelling and predictive toxicology in the safety assessment of chemicals and consumer products. The starting point will be regulatory assessment of chemicals based on their potential for harming human health or the environment. This will set the scene for describing current practices in the development and application of mathematical and computational models. A wide variety of methodological approaches are employed, ranging from relatively simple statistical models to more advanced machine learning approaches. The modelling context also ranges from discovering the underlying mechanisms of chemical toxicity to the safe and sustainable design of chemical products. The main modelling approaches will be reviewed, along with the challenges and opportunities associated with their use.  The presentation will conclude by identifying current research needs, including progress towards a Unified Theory of Chemical Toxicology.

Fri, 29 Oct 2021

14:00 - 15:00
L3

### Design and control of biochemical reaction networks

Dr Tomislav Plesa
(University of Cambridge)
Abstract

Many scientific questions in biology can be formulated as a direct problem:

given a biochemical system, can one deduce some of its properties?

For example, one might be interested in deducing equilibria of a given intracellular network.  On the other hand, one might instead be interested in designing an intracellular network with specified equilibria. Such scientific tasks take the form of inverse problems:
given a property, can one design a biochemical system that displays this property?

Given a biochemical system, can one embed additional molecular species and reactions into the original system to control some of its properties?
These questions are at the heart of the emerging field of synthetic biology, where it has recently become possible to systematically realize dynamical systems using molecules.  Furthermore, addressing these questions for man-made synthetic systems may also shed light on how evolution has overcome similar challenges for natural systems.  In this talk, I will focus on the inverse problems, and outline some of the results and challenges which are important when biochemical systems are designed and controlled.

Fri, 22 Oct 2021

14:00 - 15:00
L3

### Programmable genome regulation for studying quantitative genomics and developing high-precision therapy

Prof Stanley Qi
(Departments of Bioengineering and Chemical and Systems Biology Stanford University)
Abstract

Manipulation of the genome function is important for understanding the underlying genetics for sophisticated phenotypes and developing gene therapy. Beyond gene editing, there is a major need for high-precision and quantitative technologies that allow controlling and studying gene expression and epigenetics in the genome. Towards this goal, we develop the concept and technologies for the use of the nuclease-deactivated CRISPR-Cas (dCas) system, repurposed from the Cas nuclease, for programmable transcription regulation, epigenetic modifications, and the 3D genome organization. We combine genome engineering and mathematical modeling to understand the noncoding DNA function including ultralong-distance enhancers and repetitive elements. We actively explore new tools that allow precise manipulation of the large-scale chromatin as a novel gene therapy. In this talk, I will highlight our works at the interface between genome engineering and chromatin biology for studying the noncoding genome and related applications.

Fri, 15 Oct 2021

14:00 - 15:00
L2

### Modeling and topological data analysis for biological ring channels

Prof Veronica Ciocanel
(Duke University)
Abstract

Actin filaments are polymers that interact with myosin motor
proteins and play important roles in cell motility, shape, and
development. Depending on its function, this dynamic network of
interacting proteins reshapes and organizes in a variety of structures,
including bundles, clusters, and contractile rings. Motivated by
observations from the reproductive system of the roundworm C. elegans,
we use an agent-based modeling framework to simulate interactions
between actin filaments and myosin motor proteins inside cells. We also
develop tools based on topological data analysis to understand
time-series data extracted from these filament network interactions. We
use these tools to compare the filament organization resulting from
myosin motors with different properties. We have also recently studied
how myosin motor regulation may regulate actin network architectures
during cell cycle progression. This work also raises questions about how
to assess the significance of topological features in common topological
summary visualizations.

Fri, 18 Jun 2021

14:00 - 15:00
Virtual

### Analysis of temporal event sequences: challenges and opportunities in healthcare

Dr Maria-Cruz Villa Uriol
(Department of Computer Science The University of Sheffield)
Abstract

Our society is witnessing an exponential growth of data being generated. Among the various data types being routinely collected, event logs are available in a wide variety of domains. Despite historical and structural digitalisation challenges, healthcare is an example where the analysis of event logs might bring a new revolution.

In this talk, I will present our recent efforts in analysing and exploring temporal event data sequences extracted from event logs. Our visual analytics approach is able to summarise and seamlessly explore large volumes of complex event data sequences. We are able to easily derive observations and findings that otherwise would have required significant investment of time and effort.  To facilitate the identification of findings, we use a hierarchical clustering approach to cluster sequences according to time and a novel visualisation environment.  To control the level of detail presented to the analyst, we use a hierarchical aggregation tree and an Align-Score-Simplify strategy based on an information score.   To show the benefits of this approach, I will present our results in three real world case studies: CUREd, Outpatient clinics and MIMIC-III. These will respectively cover the analysis of calls and responses of emergency services, the efficiency of operation of two outpatient clinics, and the evolution of patients with atrial fibrillation hospitalised in an acute and critical care unit. To finalise the talk, I will share our most recent work in the analysis of clinical events extracted from Electronic Health Records for the study of multimorbidity.