Quantitative Biology - Quantitative Methods Publications (50)


Quantitative Biology - Quantitative Methods Publications

Borneo contains some of the world's most biodiverse and carbon dense tropical forest, but this 750,000-km2 island has lost 62% of its old-growth forests within the last 40 years. Efforts to protect and restore the remaining forests of Borneo hinge on recognising the ecosystem services they provide, including their ability to store and sequester carbon. Airborne Laser Scanning (ALS) is a remote sensing technology that allows forest structural properties to be captured in great detail across vast geographic areas. Read More

Evaluating expression of the Human epidermal growth factor receptor 2 (Her2) by visual examination of immunohistochemistry (IHC) on invasive breast cancer (BCa) is a key part of the diagnostic assessment of BCa due to its recognised importance as a predictive and prognostic marker in clinical practice. However, visual scoring of Her2 is subjective and consequently prone to inter-observer variability. Given the prognostic and therapeutic implications of Her2 scoring, a more objective method is required. Read More

High throughput immune repertoire sequencing is promising to lead to new statistical diagnostic tools for medicine and biology. Successful implementations of these methods require a correct characterization, analysis and interpretation of these datasets. We present IGoR -- a new comprehensive tool that takes B or T-cell receptors sequence reads and quantitatively characterizes the statistics of receptor generation from both cDNA and gDNA. Read More

The sensitivity properties of intermittent control are analysed and the conditions for a limit cycle derived theoretically and verified by simulation. Read More

Monoclonal antibodies constitute one of the most important strategies to treat patients suffering from cancers such as hematological malignancies and solid tumors. In order to guarantee the quality of those preparations prepared at hospital, quality control has to be developed. The aim of this study was to explore a noninvasive, nondestructive, and rapid analytical method to ensure the quality of the final preparation without causing any delay in the process. Read More

Pair Hidden Markov Models (PHMMs) are probabilistic models used for pairwise sequence alignment, a quintessential problem in bioinformatics. PHMMs include three types of hidden states: match, insertion and deletion. Most previous studies have used one or two hidden states for each PHMM state type. Read More

Segmentation, the process of delineating tumor apart from healthy tissue, is a vital part of both the clinical assessment and the quantitative analysis of brain cancers. Here, we provide an open-source algorithm (MITKats), built on the Medical Imaging Interaction Toolkit, to provide user-friendly and expedient tools for semi-automatic segmentation. To evaluate its performance against competing algorithms, we applied MITKats to 38 high-grade glioma cases from publicly available benchmarks. Read More

Experimental datasets for system inference often do not exhibit theoretical desiderata such as known and amenable distributions of couplings, and have no guarantee of sparse connectivity. An example is that of network reconstruction for brain networks with data from various imaging modalities. In this Letter, we introduce an entirely data-driven approach to model inference based on maximizing Shannon entropy using Schwinger's approach in the mathematical formalism of statistical physics and show model recovery in the limit of little data. Read More

Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile. Read More

Prediction of poly(lactic co glycolic acid) (PLGA) micro- and nanoparticles' dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. Read More

Due to complexity and invisibility of human organs, diagnosticians need to analyze medical images to determine where the lesion region is, and which kind of disease is, in order to make precise diagnoses. For satisfying clinical purposes through analyzing medical images, registration plays an essential role. For instance, in Image-Guided Interventions (IGI) and computer-aided surgeries, patient anatomy is registered to preoperative images to guide surgeons complete procedures. Read More

Dynamic balance in human locomotion can be assessed through the local dynamic stability (LDS) method. Whereas gait LDS has been used successfully in many settings and applications, little is known about its sensitivity to individual characteristics of healthy adults. Therefore, we reanalyzed a large dataset of accelerometric data measured for 100 healthy adults from 20 to 70 years of age performing 10 min. Read More

Accurate predictions of peptide retention times (RT) in liquid chromatography have many applications in mass spectrometry-based proteomics. Herein, we present DeepRT, a deep learning based software for peptide retention time prediction. DeepRT automatically learns features directly from the peptide sequences using the deep convolutional Neural Network (CNN) and Recurrent Neural Network (RNN) model, which eliminates the need to use hand-crafted features or rules. Read More

A large number of protein sequences are becoming available through the application of novel high-throughput sequencing technologies. Experimental functional characterization of these proteins is time-consuming and expensive, and is often only done rigorously for few selected model organisms. Computational function prediction approaches have been suggested to fill this gap. Read More

Dynamic cerebral autoregulation, that is the transient response of cerebral blood flow to changes in arterial blood pressure, is currently assessed using a variety of different time series methods and data collection protocols. In the continuing absence of a gold standard for the study of cerebral autoregulation it is unclear to what extent does the assessment depend on the choice of a computational method and protocol. We use continuous measurements of blood pressure and cerebral blood flow velocity in the middle cerebral artery from the cohorts of 18 normotensive subjects performing sit-to-stand manoeuvre. Read More

In recent years, deep learning algorithms have outperformed the state-of-the art methods in several areas thanks to the efficient methods for training and for preventing overfitting, advancement in computer hardware, the availability of vast amount data. The high performance of multi-task deep neural networks in drug discovery has attracted the attention to deep learning algorithms in bioinformatics area. Here, we proposed a hierarchical multi-task deep neural network architecture based on Gene Ontology (GO) terms as a solution to protein function prediction problem and investigated various aspects of the proposed architecture by performing several experiments. Read More

The development of chemical reaction models aids system design and optimization, along with fundamental understanding, in areas including combustion, catalysis, electrochemistry, and biology. A systematic approach to building reaction network models uses available data not only to estimate unknown parameters, but also to learn the model structure. Bayesian inference provides a natural approach to this data-driven construction of models. Read More

Developing an accurate and reliable injury prediction method is central to the biomechanics studies of traumatic brain injury. Previous efforts have relied on empirical metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific region of interest. A single "training" dataset has also been used to evaluate performance but without cross-validation. Read More

Computational models in fields such as computational neuroscience are often evaluated via stochastic simulation or numerical approximation. Fitting these models implies a difficult optimization problem over complex, possibly noisy parameter landscapes. Bayesian optimization (BO) has been successfully applied to solving expensive black-box problems in engineering and machine learning. Read More

Reducing the number of false positive discoveries is presently one of the most pressing issues in the life sciences. It is of especially great importance for many applications in neuroimaging and genomics, where datasets are typically high-dimensional, which means that the number of explanatory variables exceeds the sample size. The false discovery rate (FDR) is a criterion that can be employed to address that issue. Read More

The present paper proposes a novel computational method for parametric imaging of nuclear medicine data. The mathematical procedure is general enough to work for compartmental models of diverse complexity and is effective in the determination of the parametric maps of all kinetic parameters governing tracer flow. We consider applications to [18F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) data and analyze the two-compartment catenary model describing the standard FDG metabolization by an homogeneous tissue, e. Read More

We investigate the emergence of self-organised trails in collective motion of social organisms by means of an agent-based model. We present numerical evidences that an increase in the efficiency of navigation between the target areas, in dependence of the colony size, exists. Moreover, the shift, from the maladaptive to the adaptive behaviour, can be quantitative characterised, identifying and measuring a well defined crossover point. Read More

Background: Mining gene modules from genomic data is an important step to detect gene members of pathways or other relations such as protein-protein interactions. In this work, we explore the plausibility of detecting gene modules by factorizing gene-phenotype associations from a phenotype ontology rather than the conventionally used gene expression data. In particular, the hierarchical structure of ontology has not been sufficiently utilized in clustering genes while functionally related genes are consistently associated with phenotypes on the same path in the phenotype ontology. Read More

Mathematical models of real life phenomena are highly nonlinear involving multiple parameters and often exhibiting complex dynamics. Experimental data sets are typically small and noisy, rendering estimation of parameters from such data unreliable and difficult. This paper presents a study of the Bayesian posterior distribution for unknown parameters of two chaotic discrete dynamical systems conditioned on observations of the system. Read More

Images of living human brains can be acquired non-invasively by using magnetic resonance imaging (MRI). Different scanning parameters weight the image contrast to different tissue properties. A few examples of these differently weighted images are; T1 weighted (T1w) images to maximize the contrast between white matter and gray matter tissues, proton density weighted (PDw) for measuring concentration of hydrogen atoms and T2* weighted (T2*w) for creating a contrast highlighting the iron content. Read More

Life science is entering a new era of petabyte-level sequencing data. Converting such big data to biological insights represents a huge challenge for computational analysis. To this end, we developed DeepMetabolism, a biology-guided deep learning system to predict cell phenotypes from transcriptomics data. Read More

We provide an overview of the state-of-the-art for mathematical methods that are used to reconstruct brain activity from neurophysiological data. After a brief introduction on the mathematics of the forward problem, we discuss standard and recently proposed regularization methods, as well as Monte Carlo techniques for Bayesian inference. We classify the inverse methods based on the underlying source model, and discuss advantages and disadvantages. Read More

Recent outbreaks of Ebola, N1H1 and other infectious diseases have shown that the assumptions underlying the established theory of epidemics management are too idealistic. For an improvement of procedures and organizations involved in fighting epidemics, extended models of epidemics management are required. The necessary extensions consist in a representation of the management loop and the potential frictions influencing the loop. Read More

We present a new method for the separation of superimposed, independent, auto-correlated com- ponents from noisy multi-channel measurement. The presented method simultaneously reconstructs and separates the components, taking all channels into account and thereby increases the effective signal-to-noise ratio considerably, allowing separations even in the high noise regime. Characteristics of the measurement instruments can be included, allowing for application in complex measurement situations. Read More

Local Ca Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. Here we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Read More

In this study, we addressed the problem of genome-wide prediction accounting for partial correlation of marker effects when the partial correlation structure, or equivalently, the pattern of zeros of the precision matrix is unknown. This problem requires estimating the partial correlation structure of marker effects, that is, learning the pattern of zeros of the corresponding precision matrix, estimating its non-null entries, and incorporating the inferred concentration matrix in the prediction of marker allelic effects. To this end, we developed a set of statistical methods based on Gaussian concentration graph models (GCGM) and Gaussian directed acyclic graph models (GDAGM) that adapt the existing theory to perform covariance model selection (GCGM) or DAG selection (GDAGM) to genome-wide prediction. Read More

The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Read More

Virtual screening (VS) is widely used during computational drug discovery to reduce costs. Chemogenomics-based virtual screening (CGBVS) can be used to predict new compound-protein interactions (CPIs) from known CPI network data using several methods, including machine learning and data mining. Although CGBVS facilitates highly efficient and accurate CPI prediction, it has poor performance for prediction of new compounds for which CPIs are unknown. Read More

Introduction: Intra-organ radiation dose sensitivity is becoming increasingly relevant in clinical radiotherapy. One method for assessment involves partitioning delineated regions of interest and comparing the relative contributions or importance to clinical outcomes. We show that an intuitive method for dividing organ contours, compound (sub-)segmentation, can unintentionally lead to sub-segments with inconsistent volumes, which will bias relative importance assessment. Read More

We investigate usage of dynamic time warping (DTW) algorithm for aligning raw signal data from MinION sequencer. DTW is mostly using for fast alignment for selective sequencing to quickly determine whether a read comes from sequence of interest. We show that standard usage of DTW has low discriminative power mainly due to problem with accurate estimation of scaling parameters. Read More

Mental decline and reduced motor control are two of the most striking features associated with aging and disease. Nonlinear and fractal analyses have proved to be useful in investigating human physiological alterations with age and disease. Similar findings have not been established for less complex organisms, though. Read More

It is generally accepted that, when moving in groups, animals process information to coordinate their motion. Recent studies have begun to apply rigorous methods based on Information Theory to quantify such distributed computation. Following this perspective, we use transfer entropy to quantify dynamic information flows locally in space and time across a school of fish during directional changes around a circular tank, i. Read More

One of the primary goals of household studies of infectious disease transmission is to estimate the household secondary attack rate (SAR), the probability of direct transmission from an index case A to a susceptible household member B during A's infectious period. In a household with m susceptibles and a single index case, the number of secondary infections is often treated as a binomial(m, p) random variable where p is the SAR. This assumes that all subsequent infections in the household are transmitted directly from the index case. Read More

A fundamental question in systems biology is what combinations of mean and variance of the species present in a stochastic biochemical reaction network are attainable by perturbing the system with an external signal. To address this question, we show that the moments evolution in any generic network can be either approximated or, under suitable assumptions, computed exactly as the solution of a switched affine system. Motivated by this application, we propose a new method to approximate the reachable set of switched affine systems. Read More

The characterization of heart dynamics with a view to distinguish abnormal from normal behavior is an interesting topic in clinical sciences. Here we present an analysis of the Electro-cardiogram (ECG) signals obtained under controlled conditions from several healthy and unhealthy subjects using the framework of multifractal analysis. Our analysis differs from the conventional nonlinear analysis in that the information contained in the amplitude variations of the signal is being extracted and quantified. Read More

We address the problem of parameter estimation in models of systems biology from noisy observations. The models we consider are characterized by simultaneous deterministic nonlinear differential equations whose parameters are either taken from in vitro experiments, or are hand-tuned during the model development process to reproduces observations from the system. We consider the family of algorithms coming under the Bayesian formulation of Approximate Bayesian Computation (ABC), and show that sensitivity analysis could be deployed to quantify the relative roles of different parameters in the system. Read More

The correct prediction of protein secondary structures is one of the key issues in predicting the correct protein folded shape, which is used for determining gene function. Existing methods make use of amino acids properties as indices to classify protein secondary structures, but are faced with a significant number of misclassifications. The paper presents a technique for the classification of protein secondary structures based on protein "signal-plotting" and the use of the Fourier technique for digital signal processing. Read More

A growing amount of evidence points to the fact that many enzymes exhibit fluctuations in their catalytic activity, which are associated with conformational changes on a broad range of timescales. The experimental study of this phenomenon, termed dynamic disorder, has become possible due to advances in single-molecule enzymology measurement techniques, through which the catalytic activity of individual enzyme molecules can be tracked in time. The biological role and importance of these fluctuations in a system with a small number of enzymes such as a living cell have only recently started being explored. Read More

Aboria is a powerful and flexible C++ library for the implementation of particle-based numerical methods. The particles in such methods can represent actual particles (e.g. Read More

Recent experimental observations have shown that excluded-volume effects play an important role in reaction diffusion processes at the cellular and subcellular level. These findings have, in turn, increased interest in research focused on incorporating such effects into stochastic models that account explicitly for every single cell in the system. The high computational costs incurred by these models have motivated the development of macroscopic continuum models, in the form of partial differential equations, that can capture the microscopic effects. Read More

Vector tomography methods intend to reconstruct and visualize vector fields in restricted domains by measuring line integrals of projections of these vector fields. Here, we deal with the reconstruction of irrotational vector functions from boundary measurements. As the majority of inverse problems, vector field recovery is an ill posed in the continuous domain and therefore further assumptions, measurements and constraints should be imposed for the full vector field estimation. Read More

Plants emission of volatile organic compounds (VOCs) is involved in a wide class of ecological functions, as VOCs play a crucial role in plants interactions with biotic and abiotic factors. Accordingly, they vary widely across species and underpin differences in ecological strategy. In this paper, VOCs spontaneously emitted by 109 plant species (belonging to 56 different families) have been qualitatively and quantitatively analysed in order to classify plants species. Read More

Affiliations: 1Centre for Research in Computational and Applied Mechanics, 2Centre for Research in Computational and Applied Mechanics, 3Centre for Research in Computational and Applied Mechanics, 4Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa, 5Division of General Surgery, Department of Surgery, Groote Schuur Hospital, Cape Town, South Africa, 6Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, South Africa

A patient-specific fluid-structure interaction (FSI) model of a phase-contrast magnetic resonance angiography (PC-MRA) imaged arteriovenous fistula is presented. The numerical model is developed and simulated using a commercial multiphysics simulation package where a semi-implicit FSI coupling scheme combines a finite volume method blood flow model and a finite element method vessel wall model. A pulsatile mass-flow boundary condition is prescribed at the artery inlet of the model, and a three-element Windkessel model at the artery and vein outlets. Read More

The chemical master equation (CME) is frequently used in systems biology to quantify the effects of stochastic fluctuations that arise due to biomolecular species with low copy numbers. The CME is a system of ordinary differential equations that describes the evolution of probability density for each population vector in the state-space of the stochastic reaction dynamics. For many examples of interest, this state-space is infinite, making it difficult to obtain exact solutions of the CME. Read More

Computational prediction of membrane protein (MP) structures is very challenging partially due to lack of sufficient solved structures for homology modeling. Recently direct evolutionary coupling analysis (DCA) sheds some light on protein contact prediction and accordingly, contact-assisted folding, but DCA is effective only on some very large-sized families since it uses information only in a single protein family. This paper presents a deep transfer learning method that can significantly improve MP contact prediction by learning contact patterns and complex sequence-contact relationship from thousands of non-membrane proteins (non-MPs). Read More