Biology subjects

Sahakyan, A. B.

Publications and source records attributed to Sahakyan, A. B..

4 recordsLinked to original sources

bioRxiv2023

Quantum mechanical electronic and geometric parameters for DNA k-mers as features for machine learning

With the development of advanced predictive modelling techniques, we are witnessing a steep increase in model development initiatives in genomics that employ high-end machine learning methodologies. Of particular interest are models that predict certain genomic or biological characteristics based solely on DNA sequence information. These models, however, treat the DNA sequence as a mere collection of four, A, T, G and C, letters, thus dismissing the past physico-chemical advancements in science that can enable the use of more intricate information about nucleic acid sequences. Here, we provide a comprehensive database of quantum mechanical and geometric features for all the permutations of 7-meric DNA in their representative B, A and Z conformations. The database is generated by employing the applicable high-cost and time-consuming quantum mechanical methodologies. This can thus make it seamless to associate a wealth of novel molecular features to any DNA sequence, by scanning it with a matching k-meric window and pulling the pre-computed values from our database for further use in modelling. We demonstrate the usefulness of our deposited features through their exclusive use in developing a model for A to C mutation rate constants.

bioinformatics↗

bioRxiv2022

Generalised interrelations among mutation rates drive the genomic compliance of Chargaff's second parity rule

Chargaffs second parity rule (PR-2), where the complementary base and k-mer contents are matching within the same strand of a double stranded DNA (dsDNA), is a phenomenon that invited many explanations. The strict compliance of nearly all nuclear dsDNA to PR-2 implies that the explanation should also be similarly adamant. In this work, we revisited the possibility of mutation rates driving PR-2 compliance. Starting from the assumption-free approach, we constructed kinetic equations for unconstrained simulations. The results were analysed for their PR-2 compliance by employing symbolic regression and machine learning techniques. We arrived to a generalised set of mutation rate interrelations in place in most species that allow for their full PR-2 compliance. Importantly, our constraints explain PR-2 in genomes out of the scope of the prior explanations based on the equilibration under mutation rates with simpler no-strand-bias constraints. We thus reinstate the role of mutation rates in PR-2 through its molecular core, now shown, under our formulation, to be tolerant to previously noted strand biases and incomplete compositional equilibration. We further investigate the time for any genome to reach PR-2, showing that it is generally earlier than the compositional equilibrium, and well within the age of life on Earth.

evolutionary biology↗

bioRxiv2022

Optimus: a general purpose adaptive optimisation engine in R

MotivationMany calculations in computational biology necessitate a use of a probabilistic optimisation protocol to determine a set of parameters that capture the system at a desired state in the configurational space. Here, we developed a flexible optimisation engine in R that can be plugged to any, simple or complex, modelling initiative through a few lucid interfacing functions, to perform a seamless optimisation with rigorous parameter sampling. ResultsOptimus features an acceptance ratio simulated annealing, acceptance ratio replica exchange, and adaptive thermoregulation, thus driving a Monte Carlo optimisation process in a flexible manner, through constrained acceptance frequency but unconstrained adaptive pseudo temperature regiments. We show the applicability of our R optimiser to a wide variety of problems spanning data analyses and computational biology tasks. Availability and ImplementationOptimus is written and implemented in R, and is freely available from the http://github.com/SahakyanLab/Optimus repository. Contactaleksandr.sahakyan@imm.ox.ac.uk Supplementary InformationSupplementary information with more details, tutorials, and developer instructions is available. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/476810v1_ufig1.gif" ALT="Figure 1"> View larger version (10K): org.highwire.dtl.DTLVardef@749b4aorg.highwire.dtl.DTLVardef@17f439eorg.highwire.dtl.DTLVardef@303ad6org.highwire.dtl.DTLVardef@66dda7_HPS_FORMAT_FIGEXP M_FIG The Optimus software logo depicting two gears ("Op") that drag the system "s", trapped in a "u" minimum, through a rough solution landscape into a more favourable solution with a deeper pseudo-energy minimum ("p"). C_FIG

bioinformatics↗

bioRxiv2021

Structure-driven effects on genomic DNA damage propensity at G-quadruplex sites

Our genome contains about half a million sites capable of forming G-quadruplex (G4) structures. Such structural formations, often localised at important regulatory loci, have high capability of altering the predisposition of corresponding genomic spans to endogenous and exogenous DNA damage. In this work, we devised an approach to systematically enrich and zoom onto structure-driven effects on the propensity to undergo 9 types of DNA damage: ultraviolet radiation-induced pyrimidine-pyrimidone (6-4) photoproduct PP and cyclobutane pyrimidine dimer CPD couplings (two dyad-based subtypes in each), cisplatin-mediated G-G crosslinks, reactive oxygen species induced 8-oxoguanine damage, DNA fragmentation upon natural decay and fossilisation, breakages from artificial enzymatic cleavage and ultrasound sonication. Our results indicate that the structural effects on DNA damageability at G4 sites are not a simple combination of shielding (G4 strand) and de-shielding (opposite strand) against damaging factors, and the outcomes have different patterns and variation from one damage type to another, highly dependent on the G4 strength and relative strand localisation. The results are accompanied by electronic structure calculations, detailed structural parallels and considerations. Graphical Abstract. An illustration of the considered damage factors acting on G-quadruplex sites, through strand-specific (two pointing thunder signs) and strand-invariant (a single pointing thunder sign) manner. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/471014v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@91e464org.highwire.dtl.DTLVardef@296bc8org.highwire.dtl.DTLVardef@1635413org.highwire.dtl.DTLVardef@24b86a_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗