arXiv subjects

Sophia N. Yaliraki

Publications and source records attributed to Sophia N. Yaliraki.

At least 19 recordsLinked to original sources

arXiv2022

Prediction of protein allosteric signalling pathways and functional residues through paths of optimised propensity

Allostery commonly refers to the mechanism that regulates protein activity through the binding of a molecule at a different, usually distal, site from the orthosteric site. The omnipresence of allosteric regulation in nature and its potential for drug design and screening render the study of allostery invaluable. Nevertheless, challenges remain as few computational methods are available to effectively predict allosteric sites, identify signalling pathways involved in allostery, or to aid with the design of suitable molecules targeting such sites. Recently, bond-to-bond propensity analysis has been shown successful at identifying allosteric sites for a large and diverse group of proteins from knowledge of the orthosteric sites and its ligands alone by using network analysis applied to energy-weighted atomistic protein graphs. To address the identification of signalling pathways, we propose here a method to compute and score paths of optimised propensity that link the orthosteric site with the identified allosteric sites, and identifies crucial residues that contribute to those paths. We showcase the approach with three well-studied allosteric proteins: h-Ras, caspase-1, and 3-phosphoinositide-dependent kinase-1 (PDK1). Key residues in both orthosteric and allosteric sites were identified and showed agreement with experimental results, and pivotal signalling residues along the pathway were also revealed, thus providing alternative targets for drug design. By using the computed path scores, we were also able to differentiate the activity of different allosteric modulators.

q-bio.BM↗

arXiv2020

Graph-based Topic Extraction from Vector Embeddings of Text Documents: Application to a Corpus of News Articles

Production of news content is growing at an astonishing rate. To help manage and monitor the sheer amount of text, there is an increasing need to develop efficient methods that can provide insights into emerging content areas, and stratify unstructured corpora of text into `topics' that stem intrinsically from content similarity. Here we present an unsupervised framework that brings together powerful vector embeddings from natural language processing with tools from multiscale graph partitioning that can reveal natural partitions at different resolutions without making a priori assumptions about the number of clusters in the corpus. We show the advantages of graph-based clustering through end-to-end comparisons with other popular clustering and topic modelling methods, and also evaluate different text vector embeddings, from classic Bag-of-Words to Doc2Vec to the recent transformers based model Bert. This comparative work is showcased through an analysis of a corpus of US news coverage during the presidential election year of 2016.

cs.CL↗

arXiv2020

Data-driven modelling and characterisation of task completion sequences in online courses

The intrinsic temporality of learning demands the adoption of methodologies capable of exploiting time-series information. In this study we leverage the sequence data framework and show how data-driven analysis of temporal sequences of task completion in online courses can be used to characterise personal and group learners' behaviors, and to identify critical tasks and course sessions in a given course design. We also introduce a recently developed probabilistic Bayesian model to learn sequence trajectories of students and predict student performance. The application of our data-driven sequence-based analyses to data from learners undertaking an on-line Business Management course reveals distinct behaviors within the cohort of learners, identifying learners or groups of learners that deviate from the nominal order expected in the course. Using course grades a posteriori, we explore differences in behavior between high and low performing learners. We find that high performing learners follow the progression between weekly sessions more regularly than low performing learners, yet within each weekly session high performing learners are less tied to the nominal task order. We then model the sequences of high and low performance students using the probablistic Bayesian model and show that we can learn engagement behaviors associated with performance. We also show that the data sequence framework can be used for task centric analysis; we identify critical junctures and differences among types of tasks within the course design. We find that non-rote learning tasks, such as interactive tasks or discussion posts, are correlated with higher performance. We discuss the application of such analytical techniques as an aid to course design, intervention, and student supervision.

cs.SI↗

arXiv2020

Severability of mesoscale components and local time scales in dynamical networks

A major goal of dynamical systems theory is the search for simplified descriptions of the dynamics of a large number of interacting states. For overwhelmingly complex dynamical systems, the derivation of a reduced description on the entire dynamics at once is computationally infeasible. Other complex systems are so expansive that despite the continual onslaught of new data only partial information is available. To address this challenge, we define and optimise for a local quality function severability for measuring the dynamical coherency of a set of states over time. The theoretical underpinnings of severability lie in our local adaptation of the Simon-Ando-Fisher time-scale separation theorem, which formalises the intuition of local wells in the Markov landscape of a dynamical process, or the separation between a microscopic and a macroscopic dynamics. Finally, we demonstrate the practical relevance of severability by applying it to examples drawn from power networks, image segmentation, social networks, metabolic networks, and word association.

physics.soc-ph↗

arXiv2019

Allostery and cooperativity in multimeric proteins: bond-to-bond propensities in ATCase

Aspartate carbamoyltransferase (ATCase) is a large dodecameric enzyme with six active sites that exhibits allostery: its catalytic rate is modulated by the binding of various substrates at distal points from the active sites. A recently developed method, bond-to-bond propensity analysis, has proven capable of predicting allosteric sites in a wide range of proteins using an energy-weighted atomistic graph obtained from the protein structure and given knowledge only of the location of the active site. Bond-to-bond propensity establishes if energy fluctuations at given bonds have significant effects on any other bond in the protein, by considering their propagation through the protein graph. In this work, we use bond-to-bond propensity analysis to study different aspects of ATCase activity using three different protein structures and sources of fluctuations. First, we predict key residues and bonds involved in the transition between inactive (T) and active (R) states of ATCase by analysing allosteric substrate binding as a source of energy perturbations in the protein graph. Our computational results also indicate that the effect of multiple allosteric binding is non linear: a switching effect is observed after a particular number and arrangement of substrates is bound suggesting a form of long range communication between the distantly arranged allosteric sites. Second, cooperativity is explored by considering a bisubstrate analogue as the source of energy fluctuations at the active site, also leading to the identification of highly significant residues to the T-R transition that enhance cooperativity across active sites. Finally, the inactive (T) structure is shown to exhibit a strong, non linear communication between the allosteric sites and the interface between catalytic subunits, rather than the active site.

q-bio.QM↗

arXiv2019

Extracting information from free text through unsupervised graph-based clustering: an application to patient incident records

The large volume of text in electronic healthcare records often remains underused due to a lack of methodologies to extract interpretable content. Here we present an unsupervised framework for the analysis of free text that combines text-embedding with paragraph vectors and graph-theoretical multiscale community detection. We analyse text from a corpus of patient incident reports from the National Health Service in England to find content-based clusters of reports in an unsupervised manner and at different levels of resolution. Our unsupervised method extracts groups with high intrinsic textual consistency and compares well against categories hand-coded by healthcare personnel. We also show how to use our content-driven clusters to improve the supervised prediction of the degree of harm of the incident based on the text of the report. Finally, we discuss future directions to monitor reports over time, and to detect emerging trends outside pre-existing categories.

cs.LG↗

arXiv2019

Data-driven unsupervised clustering of online learner behaviour

The widespread adoption of online courses opens opportunities for the analysis of learner behaviour and for the optimisation of web-based material adapted to observed usage. Here we introduce a mathematical framework for the analysis of time series collected from online engagement of learners, which allows the identification of clusters of learners with similar online behaviour directly from the data, i.e., the groups of learners are not pre-determined subjectively but emerge algorithmically from the analysis and the data.The method uses a dynamic time warping kernel to create a pairwise similarity between time series of learner actions, and combines it with an unsupervised multiscale graph clustering algorithm to cluster groups of learners with similar patterns of behaviour. We showcase our approach on online engagement data of adult learners taking six web-based courses as part of a post-graduate degree at Imperial Business School. Our analysis identifies clusters of learners with statistically distinct patterns of engagement, ranging from distributed to massed learning, with different levels of adherence to pre-planned course structure and/or task completion, and also revealing outlier learners with highly sporadic behaviour. A posteriori comparison with performance showed that, although the majority of low-performing learners are part of in the massed learning cluster, the high performing learners are distributed across clusters with different traits of online engagement. We also show that our methodology is able to identify low performing learners more accurately than common classification methods based on raw statistics extracted from the data.

cs.SI↗

arXiv2018

From Free Text to Clusters of Content in Health Records: An Unsupervised Graph Partitioning Approach

Electronic Healthcare records contain large volumes of unstructured data in different forms. Free text constitutes a large portion of such data, yet this source of richly detailed information often remains under-used in practice because of a lack of suitable methodologies to extract interpretable content in a timely manner. Here we apply network-theoretical tools to the analysis of free text in Hospital Patient Incident reports in the English National Health Service, to find clusters of reports in an unsupervised manner and at different levels of resolution based directly on the free text descriptions contained within them. To do so, we combine recently developed deep neural network text-embedding methodologies based on paragraph vectors with multi-scale Markov Stability community detection applied to a similarity graph of documents obtained from sparsified text vector similarities. We showcase the approach with the analysis of incident reports submitted in Imperial College Healthcare NHS Trust, London. The multiscale community structure reveals levels of meaning with different resolution in the topics of the dataset, as shown by relevant descriptive terms extracted from the groups of records, as well as by comparing a posteriori against hand-coded categories assigned by healthcare personnel. Our content communities exhibit good correspondence with well-defined hand-coded categories, yet our results also provide further medical detail in certain areas as well as revealing complementary descriptors of incidents beyond the external classification. We also discuss how the method can be used to monitor reports over time and across different healthcare providers, and to detect emerging trends that fall outside of pre-existing categories.

cs.CL↗

arXiv2018

Content-driven, unsupervised clustering of news articles through multiscale graph partitioning

The explosion in the amount of news and journalistic content being generated across the globe, coupled with extended and instantaneous access to information through online media, makes it difficult and time-consuming to monitor news developments and opinion formation in real time. There is an increasing need for tools that can pre-process, analyse and classify raw text to extract interpretable content; specifically, identifying topics and content-driven groupings of articles. We present here such a methodology that brings together powerful vector embeddings from Natural Language Processing with tools from Graph Theory that exploit diffusive dynamics on graphs to reveal natural partitions across scales. Our framework uses a recent deep neural network text analysis methodology (Doc2vec) to represent text in vector form and then applies a multi-scale community detection method (Markov Stability) to partition a similarity graph of document vectors. The method allows us to obtain clusters of documents with similar content, at different levels of resolution, in an unsupervised manner. We showcase our approach with the analysis of a corpus of 9,000 news articles published by Vox Media over one year. Our results show consistent groupings of documents according to content without a priori assumptions about the number or type of clusters to be found. The multilevel clustering reveals a quasi-hierarchy of topics and subtopics with increased intelligibility and improved topic coherence as compared to external taxonomy services and standard topic detection methods.

cs.CL↗

arXiv2018

From Text to Topics in Healthcare Records: An Unsupervised Graph Partitioning Methodology

Electronic Healthcare Records contain large volumes of unstructured data, including extensive free text. Yet this source of detailed information often remains under-used because of a lack of methodologies to extract interpretable content in a timely manner. Here we apply network-theoretical tools to analyse free text in Hospital Patient Incident reports from the National Health Service, to find clusters of documents with similar content in an unsupervised manner at different levels of resolution. We combine deep neural network paragraph vector text-embedding with multiscale Markov Stability community detection applied to a sparsified similarity graph of document vectors, and showcase the approach on incident reports from Imperial College Healthcare NHS Trust, London. The multiscale community structure reveals different levels of meaning in the topics of the dataset, as shown by descriptive terms extracted from the clusters of records. We also compare a posteriori against hand-coded categories assigned by healthcare personnel, and show that our approach outperforms LDA-based models. Our content clusters exhibit good correspondence with two levels of hand-coded categories, yet they also provide further medical detail in certain areas and reveal complementary descriptors of incidents beyond the external classification taxonomy.

cs.CL↗

arXiv2016

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of allosteric sites is then attained in a further set of 17 proteins known to exhibit allostery. Because our propensity measure runs in almost linear time, it offers a scalable approach to high-throughput searches for candidate allosteric sites.

q-bio.BM↗

arXiv2016

Window functions and sigmoidal behaviour of memristive systems

A common approach to model memristive systems is to include empirical window functions to describe edge effects and non-linearities in the change of the memristance. We demonstrate that under quite general conditions, each window function can be associated with a sigmoidal curve relating the normalised time-dependent memristance to the time integral of the input. Conversely, this explicit relation allows us to derive window functions suitable for the mesoscopic modelling of memristive systems from a variety of well-known sigmoidals. Such sigmoidal curves are defined in terms of measured variables and can thus be extracted from input and output signals of a device and then transformed to its corresponding window. We also introduce a new generalised window function that allows the flexible modelling of asymmetric edge effects in a simple manner.

cond-mat.mes-hall↗

arXiv2014

Interest communities and flow roles in directed networks: the Twitter network of the UK riots

Directionality is a crucial ingredient in many complex networks in which information, energy or influence are transmitted. In such directed networks, analysing flows (and not only the strength of connections) is crucial to reveal important features of the network that might go undetected if the orientation of connections is ignored. We showcase here a flow-based approach for community detection in networks through the study of the network of the most influential Twitter users during the 2011 riots in England. Firstly, we use directed Markov Stability to extract descriptions of the network at different levels of coarseness in terms of interest communities, i.e., groups of nodes within which flows of information are contained and reinforced. Such interest communities reveal user groupings according to location, profession, employer, and topic. The study of flows also allows us to generate an interest distance, which affords a personalised view of the attention in the network as viewed from the vantage point of any given user. Secondly, we analyse the profiles of incoming and outgoing long-range flows with a combined approach of role-based similarity and the novel relaxed minimum spanning tree algorithm to reveal that the users in the network can be classified into five roles. These flow roles go beyond the standard leader/follower dichotomy and differ from classifications based on regular/structural equivalence. We then show that the interest communities fall into distinct informational organigrams characterised by a different mix of user roles reflecting the quality of dialogue within them. Our generic framework can be used to provide insight into how flows are generated, distributed, preserved and consumed in directed networks.

physics.soc-ph↗

arXiv2014

Structure of complex networks: Quantifying edge-to-edge relations by failure-induced flow redistribution

The analysis of complex networks has so far revolved mainly around the role of nodes and communities of nodes. However, the dynamics of interconnected systems is commonly focalised on edge processes, and a dual edge-centric perspective can often prove more natural. Here we present graph-theoretical measures to quantify edge-to-edge relations inspired by the notion of flow redistribution induced by edge failures. Our measures, which are related to the pseudo-inverse of the Laplacian of the network, are global and reveal the dynamical interplay between the edges of a network, including potentially non-local interactions. Our framework also allows us to define the embeddedness of an edge, a measure of how strongly an edge features in the weighted cuts of the network. We showcase the general applicability of our edge-centric framework through analyses of the Iberian Power grid, traffic flow in road networks, and the C. elegans neuronal network.

physics.soc-ph↗

arXiv2013

The stability of a graph partition: A dynamics-based framework for community detection

Recent years have seen a surge of interest in the analysis of complex networks, facilitated by the availability of relational data and the increasingly powerful computational resources that can be employed for their analysis. Naturally, the study of real-world systems leads to highly complex networks and a current challenge is to extract intelligible, simplified descriptions from the network in terms of relevant subgraphs, which can provide insight into the structure and function of the overall system. Sparked by seminal work by Newman and Girvan, an interesting line of research has been devoted to investigating modular community structure in networks, revitalising the classic problem of graph partitioning. However, modular or community structure in networks has notoriously evaded rigorous definition. The most accepted notion of community is perhaps that of a group of elements which exhibit a stronger level of interaction within themselves than with the elements outside the community. This concept has resulted in a plethora of computational methods and heuristics for community detection. Nevertheless a firm theoretical understanding of most of these methods, in terms of how they operate and what they are supposed to detect, is still lacking to date. Here, we will develop a dynamical perspective towards community detection enabling us to define a measure named the stability of a graph partition. It will be shown that a number of previously ad-hoc defined heuristics for community detection can be seen as particular cases of our method providing us with a dynamic reinterpretation of those measures. Our dynamics-based approach thus serves as a unifying framework to gain a deeper understanding of different aspects and problems associated with community detection and allows us to propose new dynamically-inspired criteria for community structure.

physics.soc-ph↗

arXiv2012

Markov dynamics as a zooming lens for multiscale community detection: non clique-like communities and the field-of-view limit

In recent years, there has been a surge of interest in community detection algorithms for complex networks. A variety of computational heuristics, some with a long history, have been proposed for the identification of communities or, alternatively, of good graph partitions. In most cases, the algorithms maximize a particular objective function, thereby finding the `right' split into communities. Although a thorough comparison of algorithms is still lacking, there has been an effort to design benchmarks, i.e., random graph models with known community structure against which algorithms can be evaluated. However, popular community detection methods and benchmarks normally assume an implicit notion of community based on clique-like subgraphs, a form of community structure that is not always characteristic of real networks. Specifically, networks that emerge from geometric constraints can have natural non clique-like substructures with large effective diameters, which can be interpreted as long-range communities. In this work, we show that long-range communities escape detection by popular methods, which are blinded by a restricted `field-of-view' limit, an intrinsic upper scale on the communities they can detect. The field-of-view limit means that long-range communities tend to be overpartitioned. We show how by adopting a dynamical perspective towards community detection (Delvenne et al. (2010) PNAS:107: 12755-12760; Lambiotte et al. (2008) arXiv:0812.1770), in which the evolution of a Markov process on the graph is used as a zooming lens over the structure of the network at all scales, one can detect both clique- or non clique-like communities without imposing an upper scale to the detection. Consequently, the performance of algorithms on inherently low-diameter, clique-like benchmarks may not always be indicative of equally good results in real networks with local, sparser connectivity.

physics.soc-ph↗

arXiv2011

Quantitative Measure of Hysteresis for Memristors Through Explicit Dynamics

We introduce a mathematical framework for the analysis of the input-output dynamics of externally driven memristors. We show that, under general assumptions, their dynamics comply with a Bernoulli differential equation and hence can be nonlinearly transformed into a formally solvable linear equation. The Bernoulli formalism, which applies to both charge- and flux-controlled memristors when either current- or voltage-driven, can, in some cases, lead to expressions of the output of the device as an explicit function of the input. We apply our framework to obtain analytical solutions of the i-v characteristics of the recently proposed model of the Hewlett-Packard memristor under three different drives without the need for numerical simulations. Our explicit solutions allow us to identify a dimensionless lumped parameter that combines device-specific parameters with properties of the input drive. This parameter governs the memristive behavior of the device and, consequently, the amount of hysteresis in the i-v. We proceed further by defining formally a quantitative measure for the hysteresis of the device for which we obtain explicit formulas in terms of the aforementioned parameter and we discuss the applicability of the analysis for the design and analysis of memristor devices.

cond-mat.mes-hall↗

arXiv2006

Stochastic kinetics of viral capsid assembly based on detailed protein structures

We present a generic computational framework for the simulation of viral capsid assembly which is quantitative and specific. Starting from PDB files containing atomic coordinates, the algorithm builds a coarse grained description of protein oligomers based on graph rigidity. These reduced protein descriptions are used in an extended Gillespie algorithm to investigate the stochastic kinetics of the assembly process. The association rates are obtained from a diffusive Smoluchowski equation for rapid coagulation, modified to account for water shielding and protein structure. The dissociation rates are derived by interpreting the splitting of oligomers as a process of graph partitioning akin to the escape from a multidimensional well. This modular framework is quantitative yet computationally tractable, with a small number of physically motivated parameters. The methodology is illustrated using two different viruses which are shown to follow quantitatively different assembly pathways. We also show how in this model the quasi-stationary kinetics of assembly can be described as a Markovian cascading process in which only a few intermediates and a small proportion of pathways are present. The observed pathways and intermediates can be related a posteriori to structural and energetic properties of the capsid oligomers.

q-bio.QM↗