New articles on Quantitative Biology

[1] 2107.12536

A Data-Driven Biophysical Computational Model of Parkinson's Disease based on Marmoset Monkeys

In this work we propose a new biophysical computational model of brain regions relevant to Parkinson's Disease based on local field potential data collected from the brain of marmoset monkeys. Parkinson's disease is a neurodegenerative disorder, linked to the death of dopaminergic neurons at the substantia nigra pars compacta, which affects the normal dynamics of the basal ganglia-thalamus-cortex neuronal circuit of the brain. Although there are multiple mechanisms underlying the disease, a complete description of those mechanisms and molecular pathogenesis are still missing, and there is still no cure. To address this gap, computational models that resemble neurobiological aspects found in animal models have been proposed. In our model, we performed a data-driven approach in which a set of biologically constrained parameters is optimised using differential evolution. Evolved models successfully resembled single-neuron mean firing rates and spectral signatures of local field potentials from healthy and parkinsonian marmoset brain data. As far as we are concerned, this is the first computational model of Parkinson's Disease based on simultaneous electrophysiological recordings from seven brain regions of Marmoset monkeys. Results show that the proposed model could facilitate the investigation of the mechanisms of PD and support the development of techniques that can indicate new therapies. It could also be applied to other computational neuroscience problems in which biological data could be used to fit multi-scale models of brain circuits.

[2] 2107.12785

A mechanistic model for airborne and direct human-to-human transmission of COVID-19: Effect of mitigation strategies and immigration of infectious persons

The COVID-19 pandemic is the most significant global crisis since World War II that affected almost all the countries of our planet. To control the COVID-19 pandemic outbreak, it is necessary to understand how the virus is transmitted to a susceptible individual and eventually spread in the community. The primary transmission pathway of COVID-19 is human-to-human transmission through infectious droplets. However, a recent study by Greenhalgh et al. (Lancet: 397:1603-1605, 2021) demonstrates 10 scientific reasons behind the airborne transmission of SARS-COV-2. In the present study, we introduce a novel mathematical model of COVID-19 that considers the transmission of free viruses in the air besides the transmission of direct contact with an infected person. The basic reproduction number of the epidemic model is calculated using the next-generation operator method and observed that it depends on both the transmission rate of direct contact and free virus contact. The local and global stability of disease-free equilibrium (DFE) is well established. Analytically it is found that there is a forward bifurcation between the DFE and an endemic equilibrium using central manifold theory. Next, we used the nonlinear least-squares technique to identify the best-fitted parameter values in the model from the observed COVID-19 mortality data of two major districts of India. Using estimated parameters for Bangalore urban and Chennai, different control scenarios for mitigation of the disease are investigated. Results indicate that when a vaccine crisis is there, the public health authorities should prefer to vaccinate the susceptible people compared to the recovered persons who are now healthy. Along with face mask use, treatment of hospitalized patients and vaccination of susceptibles, immigration should be allowed in a supervised manner so that economy of the overall society remains healthy.

[3] 2107.12799

New Candidates for Furin Inhibition as Probable Treat for COVID-19: Docking Output

Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses like the newly emerging SARS-CoV-2 virus that causes COVID-19 disease with a high rate of virulence and mortality. Unlike viral enzymes, furin owns a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs from different classes including antiviral, antibiotics, and anti protozoa/anti parasites with suspected beneficial effects on COVID-19, as ligands we have carried out docking experiments in HEX software to pickup those capable to bind furin active site with high affinity and suggest them as probable candidates for clinical trials assessments. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with cumulative inhibitory effects of 2.52, 2.16, and 2.13 respectively seem to be the best candidates for furin inhibition even in severe cases of COVID-19 as adjuvant therapy, while clarithromycin, niclosamide, and erythromycin with cumulative inhibitory indices of 1.97, 1.90, and 1.84 respectively with lower side effects than antiviral drugs could be suggested as prophylaxes for the first stage of COVID-19 as a promising treat.

[4] 2107.12817

Bam-readcount -- rapid generation of basepair-resolution sequence metrics

Bam-readcount is a utility for generating low-level information about sequencing data at specific nucleotide positions. Originally designed to help filter genomic mutation calls, the metrics it outputs are useful as input for variant detection tools and for resolving ambiguity between variant callers . In addition, it has found broad applicability in diverse fields including tumor evolution, single-cell genomics, climate change ecology, and tracking community spread of SARS-CoV-2. Here we report on the release of version 1.0 of this tool, which adds CRAM support, among other improvements. It is released under a permissive MIT license and available at

[5] 2107.12838

Graph Autoencoders for Embedding Learning in Brain Networks and Major Depressive Disorder Identification

Brain functional connectivity (FC) reveals biomarkers for identification of various neuropsychiatric disorders. Recent application of deep neural networks (DNNs) to connectome-based classification mostly relies on traditional convolutional neural networks using input connectivity matrices on a regular Euclidean grid. We propose a graph deep learning framework to incorporate the non-Euclidean information about graph structure for classifying functional magnetic resonance imaging (fMRI)- derived brain networks in major depressive disorder (MDD). We design a novel graph autoencoder (GAE) architecture based on the graph convolutional networks (GCNs) to embed the topological structure and node content of large-sized fMRI networks into low-dimensional latent representations. In network construction, we employ the Ledoit-Wolf (LDW) shrinkage method to estimate the high-dimensional FC metrics efficiently from fMRI data. We consider both supervised and unsupervised approaches for the graph embedded learning. The learned embeddings are then used as feature inputs for a deep fully-connected neural network (FCNN) to discriminate MDD from healthy controls. Evaluated on a resting-state fMRI MDD dataset with 43 subjects, results show that the proposed GAE-FCNN model significantly outperforms several state-of-the-art DNN methods for brain connectome classification, achieving accuracy of 72.50% using the LDW-FC metrics as node features. The graph embeddings of fMRI FC networks learned by the GAE also reveal apparent group differences between MDD and HC. Our new framework demonstrates feasibility of learning graph embeddings on brain networks to provide discriminative information for diagnosis of brain disorders.

[6] 2107.12901

Channel Capacity of Starch and Glucose Molecular Communications in the Small Intestine Digestive Tract

The emerging field of Molecular Communication (MC) aims to characterize biological-based signaling environment through information that are encoded into molecules. Since the birth of this field, a number of different applications and biological systems have been characterized using MC theory. This study proposes a new application and direction for MC, focusing on the digestive system, where we characterize and model the starch and glucose propagation along the small intestine. Based on the advection-diffusion and reaction mechanisms, we define a channel capacity for the small intestine digestive tract that is dependent on the starch to glucose conversion, velocity flow within the tract, viscosity of the digest product, and length of the tract and position of the receivers for glucose absorption. The numerical results from the derived channel capacity model shows that the SI digestive capacity depends both on physiological factors of the digestive system and type of consumed food, where the digestive capacity is greater for shorter gastric emptying time, low viscosity of the digest product and efficient enzyme activity. We believe that our digital MC model of the digestive tract and lead to personalized diet for each individual, which can potentially avoid a number of different diseases (e.g., celiac disease).

[7] 2107.12375

Geometric Deep Learning on Molecular Representations

Geometric deep learning (GDL), which is based on neural network architectures that incorporate and process symmetry information, has emerged as a recent paradigm in artificial intelligence. GDL bears particular promise in molecular modeling applications, in which various molecular representations with different symmetry properties and levels of abstraction exist. This review provides a structured and harmonized overview of molecular GDL, highlighting its applications in drug discovery, chemical synthesis prediction, and quantum chemistry. Emphasis is placed on the relevance of the learned molecular features and their complementarity to well-established molecular descriptors. This review provides an overview of current challenges and opportunities, and presents a forecast of the future of GDL for molecular sciences.

[8] 2107.12609

Tracking Fast Neural Adaptation by Globally Adaptive Point Process Estimation for Brain-Machine Interface

Brain-machine interfaces (BMIs) help the disabled restore body functions by translating neural activity into digital commands to control external devices. Neural adaptation, where the brain signals change in response to external stimuli or movements, plays an important role in BMIs. When subjects purely use neural activity to brain-control a prosthesis, some neurons will actively explore a new tuning property to accomplish the movement task. The prediction of this neural tuning property can help subjects adapt more efficiently to brain control and maintain good decoding performance. Existing prediction methods track the slow change of the tuning property in the manual control, which is not suitable for the fast neural adaptation in brain control. In order to identify the active neurons in brain control and track their tuning property changes, we propose a globally adaptive point process method (GaPP) to estimate the neural modulation state from spike trains, decompose the states into the hyper preferred direction and reconstruct the kinematics in a dual-model framework. We implement the method on real data from rats performing a two-lever discrimination task under manual control and brain control. The results show our method successfully predicts the neural modulation state and identifies the neurons that become active in brain control. Compared to existing methods, ours tracks the fast changes of the hyper preferred direction from manual control to brain control more accurately and efficiently and reconstructs the kinematics better and faster.

[9] 2107.12979

Predictive Coding: a Theoretical and Experimental Review

Predictive coding offers a potentially unifying account of cortical function -- postulating that the core function of the brain is to minimize prediction errors with respect to a generative model of the world. The theory is closely related to the Bayesian brain framework and, over the last two decades, has gained substantial influence in the fields of theoretical and cognitive neuroscience. A large body of research has arisen based on both empirically testing improved and extended theoretical and mathematical models of predictive coding, as well as in evaluating their potential biological plausibility for implementation in the brain and the concrete neurophysiological and psychological predictions made by the theory. Despite this enduring popularity, however, no comprehensive review of predictive coding theory, and especially of recent developments in this field, exists. Here, we provide a comprehensive review both of the core mathematical structure and logic of predictive coding, thus complementing recent tutorials in the literature. We also review a wide range of classic and recent work within the framework, ranging from the neurobiologically realistic microcircuits that could implement predictive coding, to the close relationship between predictive coding and the widely-used backpropagation of error algorithm, as well as surveying the close relationships between predictive coding and modern machine learning techniques.