Biology subjects

Anantram, M. P.

Publications and source records attributed to Anantram, M. P..

3 recordsLinked to original sources

bioRxiv2024

A ML Framework for Genetic Sequence Identification using 2D Electrical Conductance Probability Distributions from Mixed Data Sets

Genetic sequence identification from electrical characterization of single molecules has emerged as a promising alternative to traditional approaches. Since electrical data on single molecules is extremely noisy due to the limitations of even state-of-the-art approaches, achieving high detection rates is challenging, particularly when the task involves being able to distinguish a sequence from its single base-pair mismatches. To address this issue, we propose an architecture based on combining a convolutional neural network with an ensemble learning method, XGBoost. In addition, four different input feature representations are considered, 1D conductance probability distributions and 2D conductance versus distance probability distributions which can be viewed as images, with or without averaging over the experimental parameters. The with averaging case corresponds to feature matrices derived from mixed datasets. We find that 2D probability distributions are helpful with respect to classifier accuracy, but averaged conductance probability distributions are much more impactful and significantly enhance prediction accuracy. Our quantitative analysis of multiple sequences shows an impressive performance increase of approximately 10% for all sequences. While the basis of our analysis is conductance data of DNA strands for COVID-19 Alpha, Beta, and Delta variants and their single base-pair mismatches, our method is generally applicable to other single-molecule identification based on their conductance.

bioinformatics↗

bioRxiv2023

A Computational Study of the Role of Counterions and Solvent Dielectric in Determining the Conductance of B-DNA

DNA naturally exists in a solvent environment, comprised of water and salt molecules such as sodium, potassium, magnesium, etc. Along with the sequence, the solvent conditions become a vital factor determining DNA structure and thus its conductance. Over the last two decades, researchers have measured DNA conductivity both in hydrated and almost dry (dehydrated) conditions. However, due to experimental limitations (the precise control of the environment), it is very difficult to analyze the conductance results in terms of individual contributions of the environment. Therefore, modeling studies can help us to gain a valuable understanding of various factors playing a role in charge transport phenomena. DNA naturally has negative charges located at the phosphate groups in the backbone, which provides both the connections between the base pairs and the structural support for the double helix. Positively charged ions such as the Sodiumion (Na+), one of the most commonly used counterions, balance the negative charges at the backbone. This modeling study investigates the role of counterions both with and without the solvent (water) environment on charge transport through double-stranded DNA. Our computational experiments show that in dry DNA, the presence of counterions affects electron transmission at the lowest unoccupied molecular orbital energies. However, in solution, the counterions have a negligible role in transmission. Using the polarizable continuum model calculations, we demonstrate that the transmission is significantly higher at both the highest occupied and lowest unoccupied molecular orbital energies in a water environment as opposed to in a dry one. Moreover, calculations also show that the energy levels of neighboring bases are more closely aligned to ease electron flow in the solution.

biophysics↗

bioRxiv2023

DNA nanopores as artificial membrane channels for origami based bioelectronics

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition1-4. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout5-8. This challenge at the biotic-abiotic interface results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices9. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces that resolve the iono-electronic disparity between the biotic environment and electronics. Through simulations and experiments, we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioelectronic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin, without disrupting the native environment of the biomolecule. We anticipate this robust biotic-abiotic interface will allow facile electronic measurement of inter-cellular ionic communication and also open the door for active control of cell behavior through externally controlled selective gating of the channels.

bioengineering↗