Structural representations of DNA regulatory substrates can enhance sequence-based algorithms by associating functional sequence variants

The nucleotide sequence representation of DNA can be inadequate for resolving protein-DNA binding sites and regulatory substrates, such as those involved in gene expression and horizontal gene transfer. Considering that sequence-like representations are algorithmically very useful, here we fused over 60 currently available DNA physicochemical and conformational variables into compact structural representations that can encode single DNA binding sites to whole regulatory regions. We find that the main structural components reflect key properties of protein-DNA interactions and can be condensed to the amount of information found in a single nucleotide position. The most accurate structural representations compress functional DNA sequence variants by 30% to 50%, as each instance encodes from tens to thousands of sequences. We show that a structural distance function discriminates among groups of DNA substrates more accurately than nucleotide sequence-based metrics. As this opens up a variety of implementation possibilities, we develop and test a distance-based alignment algorithm, demonstrating the potential of using the structural representations to enhance sequence-based algorithms. Due to the bias of most current bioinformatic methods to nucleotide sequence representations, it is possible that considerable performance increases might still be achievable with such solutions.Comment: 20 pages, 8 figures, 3 tables, conferenc

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

Optimization of Thermal and Structural Design in Lithium-Ion Batteries to Obtain Energy Efficient Battery Thermal Management System (BTMS): A Critical Review

Covid-19 has given one positive perspective to look at our planet earth in terms of reducing the air and noise pollution thus improving the environmental conditions globally. This positive outcome of pandemic has given the indication that the future of energy belong to green energy and one of the emerging source of green energy is Lithium-ion batteries (LIBs). LIBs are the backbone of the electric vehicles but there are some major issues faced by the them like poor thermal performance, thermal runaway, fire hazards and faster rate of discharge under low and high temperature environment,. Therefore to overcome these problems most of the researchers have come up with new methods of controlling and maintaining the overall thermal performance of the LIBs. The present review paper mainly is focused on optimization of thermal and structural design parameters of the LIBs under different BTMSs. The optimized BTMS generally demonstrated in this paper are maximum temperature of battery cell, battery pack or battery module, temperature uniformity, maximum or average temperature difference, inlet temperature of coolant, flow velocity, and pressure drop. Whereas the major structural design optimization parameters highlighted in this paper are type of flow channel, number of channels, length of channel, diameter of channel, cell to cell spacing, inlet and outlet plenum angle and arrangement of channels. These optimized parameters investigated under different BTMS heads such as air, PCM (phase change material), mini-channel, heat pipe, and water cooling are reported profoundly in this review article. The data are categorized and the results of the recent studies are summarized for each method. Critical review on use of various optimization algorithms (like ant colony, genetic, particle swarm, response surface, NSGA-II, etc.) for design parameter optimization are presented and categorized for different BTMS to boost their objectives. The single objective optimization techniques helps in obtaining the optimal value of important design parameters related to the thermal performance of battery cooling systems. Finally, multi-objective optimization technique is also discussed to get an idea of how to get the trade-off between the various conflicting parameters of interest such as energy, cost, pressure drop, size, arrangement, etc. which is related to minimization and thermal efficiency/performance of the battery system related to maximization. This review will be very helpful for researchers working with an objective of improving the thermal performance and life span of the LIBs.Deanship of Scientific Research at King Khalid University [GRP/129/42]Deanship of Scientific Research at King Khalid University, grant no. GRP/129/42.WOS:0006443758000012-s2.0-85105359419PubMed: 3393548