Using Chaos-Game-Representation for Analysing the SARS-CoV-2 Lineages, Newly Emerging Strains and Recombinants.

Background: Viruses have high mutation rates, facilitating rapid evolution and the emergence of new species, subspecies, strains and recombinant forms. Accurate classification of these forms is crucial for understanding viral evolution and developing therapeutic applications. Phylogenetic classification is typically performed by analyzing molecular differences at the genomic and sub-genomic levels.

A systems level approach to study metabolic networks in prokaryotes with the aromatic amino acid biosynthesis pathway.

Metabolism of an organism underlies its phenotype, which depends on many factors, such as the genetic makeup, habitat, and stresses to which it is exposed. This is particularly important for the prokaryotes, which undergo significant vertical and horizontal gene transfers. In this study we have used the energy-intensive Aromatic Amino Acid (Tryptophan, Tyrosine and Phenylalanine, TTP) biosynthesis pathway, in a large number of prokaryotes, as a model system to query the different levels of organization of metabolism in the whole intracellular biochemical network, and to understand how perturbations, such as mutations, affects the metabolic flux through the pathway - in isolation and in the context of other pathways connected to it.

Small Conformational Changes Underlie Evolution of Resistance to NNRTI in HIV Reverse Transcriptase.

Despite achieving considerable success in reducing the number of fatalities due to acquired immunodeficiency syndrome, emergence of resistance against the reverse transcriptase (RT) inhibitor drugs remains one of the biggest challenges of the human immunodeficiency virus antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) form a large class of drugs and a crucial component of ART. In NNRTIs, even a single resistance mutation is known to make the drugs completely ineffective.

Complex network analysis of thermostable mutants of Lipase A.

Three-dimensional structures of proteins that regulate their functions can be modelled using complex network based approaches for understanding the structure-function relationship. The six mutants of the protein Lipase A from , harbouring 2 to 12 mutations, retain their function at higher temperatures with negligible variation in their overall three-dimensional crystallographic structures. This enhanced thermostability of the mutants questions the structure-function paradigm.

Uncoupling of an ammonia channel as a mechanism of allosteric inhibition in anthranilate synthase of Serratia marcescens: dynamic and graph theoretical analysis.

Anthranilate synthase (AS) is the first branch node enzyme that catalyzes the conversion of chorismate to anthranilate in the high energy-consuming tryptophan biosynthetic pathway in Serratia marcescens. AS, with an allosterically-bound inhibitor (tryptophan), shows complete inhibition in its catalytic function, but the inhibitor-bound structure is very similar to that of the substrate-bound AS. Even though the reaction mechanisms of several chorismate-utilizing enzymes are known, the unusual structure-function relationship in catalysis and allosteric inhibition of AS by tryptophan, with an insignificant change in structure, remains elusive.

Thermostability of in vitro evolved Bacillus subtilis lipase A: a network and dynamics perspective.

Proteins in thermophilic organisms remain stable and function optimally at high temperatures. Owing to their important applicability in many industrial processes, such thermostable proteins have been studied extensively, and several structural factors attributed to their enhanced stability. How these factors render the emergent property of thermostability to proteins, even in situations where no significant changes occur in their three-dimensional structures in comparison to their mesophilic counter-parts, has remained an intriguing question.

Evolution of tryptophan biosynthetic pathway in microbial genomes: a comparative genetic study.

Biosynthetic pathway evolution needs to consider the evolution of a group of genes that code for enzymes catalysing the multiple chemical reaction steps leading to the final end product. Tryptophan biosynthetic pathway has five chemical reaction steps that are highly conserved in diverse microbial genomes, though the genes of the pathway enzymes show considerable variations in arrangements, operon structure (gene fusion and splitting) and regulation. We use a combined bioinformatic and statistical analyses approach to address the question if the pathway genes from different microbial genomes, belonging to a wide range of groups, show similar evolutionary relationships within and between them.

Analysis of dinucleotide signatures in HIV-1 subtype B genomes.

Dinucleotide usage is known to vary in the genomes of organisms. The dinucleotide usage profiles or genome signatures are similar for sequence samples taken from the same genome, but are different for taxonomically distant species. This concept of genome signatures has been used to study several organisms including viruses, to elucidate the signatures of evolutionary processes at the genome level.

A realistic host-vector transmission model for describing malaria prevalence pattern.

Malaria continues to be a major public health concern all over the world even after effective control policies have been employed, and considerable understanding of the disease biology have been attained, from both the experimental and modelling perspective. Interactions between different general and local processes, such as dependence on age and immunity of the human host, variations of temperature and rainfall in tropical and sub-tropical areas, and continued presence of asymptomatic infections, regulate the host-vector interactions, and are responsible for the continuing disease prevalence pattern.In this paper, a general mathematical model of malaria transmission is developed considering short and long-term age-dependent immunity of human host and its interaction with pathogen-infected mosquito vector.

Differential trends in the codon usage patterns in HIV-1 genes.

Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host-pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms.

Multifractal analysis of HIV-1 genomes.

Pathogens like HIV-1, which evolve into many closely related variants displaying differential infectivity and evolutionary dynamics in a short time scale, require fast and accurate classification. Conventional whole genome sequence alignment-based methods are computationally expensive and involve complex analysis. Alignment-free methodologies are increasingly being used to effectively differentiate genomic variations between viral species.

Mathematical models of malaria--a review.

Mathematical models have been used to provide an explicit framework for understanding malaria transmission dynamics in human population for over 100 years. With the disease still thriving and threatening to be a major source of death and disability due to changed environmental and socio-economic conditions, it is necessary to make a critical assessment of the existing models, and study their evolution and efficacy in describing the host-parasite biology. In this article, starting from the basic Ross model, the key mathematical models and their underlying features, based on their specific contributions in the understanding of spread and transmission of malaria have been discussed.

Design of regulation and dynamics in simple biochemical pathways.

Complex regulation of biochemical pathways in a cell is brought about by the interaction of simpler regulatory structures. Among the basic regulatory designs, feedback inhibition of gene expression is the most common motif in gene regulation and a ubiquitous control structure found in nature. In this work, we have studied a common structural feature (delayed feedback) in gene organisation and shown, both theoretically and experimentally, its subtle but important functional role in gene expression kinetics in a negatively auto-regulated system.

Using genomic signatures for HIV-1 sub-typing.

Background: Human Immunodeficiency Virus type 1 (HIV-1), the causative agent of Acquired Immune Deficiency Syndrome (AIDS), exhibits very high genetic diversity with different variants or subtypes prevalent in different parts of the world. Proper classification of the HIV-1 subtypes, displaying differential infectivity, plays a major role in monitoring the epidemic and is also a critical component for effective treatment strategy. The existing methods to classify HIV-1 sequence subtypes, based on phylogenetic analysis focusing only on specific genes/regions, have shown inconsistencies as they lack the capability to analyse whole genome variations.

Delay-induced transient increase and heterogeneity in gene expression in negatively auto-regulated gene circuits.

A generic feature in all intracellular biochemical processes is the time required to complete the whole sequence of reactions to yield any observable quantity--from gene expression to circadian rhythms. This widespread phenomenon points towards the importance of time delay in biological functions. Theoretically time delay is known to be the source of instability, and has been attributed to lead to oscillations or transient dynamics in several biological functions.

Measuring collective behaviour of multicellular ensembles: role of space-time scales.

Living systems are spectacular examples of spatiotemporally organized structures. During the development of complex organization there is dynamic equilibrium between the local and global processes acting at the intra-and intercellular levels in multiple space and time scales. Although in modelling studies such spatiotemporal systems can be described by different space-time scales and at many organizational levels, the experimental quantities measured and predictions useful for practical applications are at a macroscopic (coarser or averaged) level/scale; these are limited by the resolution of the measuring method and experimental protocol.

Assortative mixing in Protein Contact Networks and protein folding kinetics.

Motivation: Starting from linear chains of amino acids, the spontaneous folding of proteins into their elaborate 3D structures is one of the remarkable examples of biological self-organization. We investigated native state structures of 30 single-domain, two-state proteins, from complex networks perspective, to understand the role of topological parameters in proteins' folding kinetics, at two length scales--as 'Protein Contact Networks (PCNs)' and their corresponding 'Long-range Interaction Networks (LINs)' constructed by ignoring the short-range interactions.

Results: Our results show that, both PCNs and LINs exhibit the exceptional topological property of 'assortative mixing' that is absent in all other biological and technological networks studied so far.

Propagation of extrinsic perturbation in a negatively auto-regulated pathway.

The apparent precision of the output in multi-step biochemical pathways in the face of external and intrinsic perturbations is non-obvious and conceptually difficult. Using a simple three-step negatively auto-regulated model pathway, we show that the effect of perturbation at different steps of the pathway and its transmission through the network is dependent on the context (i.e.

The role of virus infection in a simple phytoplankton zooplankton system.

Many planktonic species show spectacular bursts ("blooms") in population density. Though viral infections are known to cause behavioural and other changes in phytoplankton and other aquatic species, yet their role in regulating the phytoplankton population is still far from being understood. To study the role of viral diseases in the planktonic species, we model the phytoplankton-zooplankton system as a prey-predator system.

Controlling dynamics in spatially extended systems.

Spatially extended systems exhibit a variety of spatiotemporal dynamics--from stable to chaotic. These dynamics can change under pathological conditions and impair normal functions. Thus, having the ability to control the altered dynamics for improved functioning has the potential for wide ranging applications in real and artificial systems.

Hydra pattern is controlled by two distinct but interacting morphogen sets.

Temporal course of regeneration of the hypostome and basal disc along the body length of the hydra is studied both in the presence and absence of the other determined centre. The regeneration times vary nonlinearly with distance from the original position indicating that the underlying processes are of non-linear nature. The presence of hypostome influences the regeneration of basal disc in an inhibitory manner throughout the body length, whereas, basal disc influences the regeneration of hypostome only in the lower portion of the body in a positive manner.