arXiv subjects

Vijay Rajagopal

Publications and source records attributed to Vijay Rajagopal.

4 recordsLinked to original sources

arXiv2022

The Cell Physiome: What do we need in a computational physiology framework for predicting single cell biology?

Modern biology and biomedicine are undergoing a big-data explosion needing advanced computational algorithms to extract mechanistic insights on the physiological state of living cells. We present the motivation for the Cell Physiome: a framework and approach for creating, sharing, and using biophysics-based computational models of single cell physiology. Using examples in calcium signaling, bioenergetics, and endosomal trafficking, we highlight the need for spatially detailed, biophysics-based computational models to uncover new mechanisms underlying cell biology. We review progress and challenges to date towards creating cell physiome models. We then introduce bond graphs as an efficient way to create cell physiome models that integrate chemical, mechanical, electromagnetic, and thermal processes while maintaining mass and energy balance. Bond graphs enhance modularization and re-usability of computational models of cells at scale. We conclude with a look forward into steps that will help fully realize this exciting new field of mechanistic biomedical data science.

q-bio.CB↗

arXiv2020

Ca2+ release via IP3 receptors shapes the cytosolic Ca2+ transient for hypertrophic signalling in ventricular cardiomyocytes

Calcium (Ca2+) plays a central role in mediating both contractile function and hypertrophic signalling in ventricular cardiomyocytes. L-type Ca2+ channels trigger release of Ca2+ from ryanodine receptors (RyRs) for cellular contraction, while signalling downstream of Gq coupled receptors stimulates Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP3Rs), engaging hypertrophic signalling pathways. Modulation of the amplitude, duration, and duty cycle of the cytosolic Ca2+ contraction signal, and spatial localisation, have all been proposed to encode this hypertrophic signal. Given current knowledge of IP3Rs, we develop a model describing the effect of functional interaction (cross-talk) between RyR and IP3R channels on the Ca2+ transient, and examine the sensitivity of the Ca2+ transient shape to properties of IP3R activation. A key result of our study is that IP3R activation increases Ca2+ transient duration for a broad range of IP3R properties, but the effect of IP3R activation on Ca2+ transient amplitude is dependent on IP3 concentration. Furthermore we demonstrate that IP3-mediated Ca2+ release in the cytosol increases the duty cycle of the Ca2+ transient, the fraction of the cycle for which [Ca2+] is elevated, across a broad range of parameter values and IP3 concentrations. When coupled to a model of downstream transcription factor (NFAT) activation, we demonstrate that there is a high correspondence between the Ca transient duty cycle and the proportion of activated NFAT in the nucleus. These findings suggest increased cytosolic Ca2+ duty cycle as a plausible mechanism for IP3-dependent hypertrophic signalling via Ca2+-sensitive transcription factors such as NFAT in ventricular cardiomyocytes.

q-bio.SC↗

arXiv2018

Reference environments: A universal tool for reproducibility in computational biology

The drive for reproducibility in the computational sciences has provoked discussion and effort across a broad range of perspectives: technological, legislative/policy, education, and publishing. Discussion on these topics is not new, but the need to adopt standards for reproducibility of claims made based on computational results is now clear to researchers, publishers and policymakers alike. Many technologies exist to support and promote reproduction of computational results: containerisation tools like Docker, literate programming approaches such as Sweave, knitr, iPython or cloud environments like Amazon Web Services. But these technologies are tied to specific programming languages (e.g. Sweave/knitr to R; iPython to Python) or to platforms (e.g. Docker for 64-bit Linux environments only). To date, no single approach is able to span the broad range of technologies and platforms represented in computational biology and biotechnology. To enable reproducibility across computational biology, we demonstrate an approach and provide a set of tools that is suitable for all computational work and is not tied to a particular programming language or platform. We present published examples from a series of papers in different areas of computational biology, spanning the major languages and technologies in the field (Python/R/MATLAB/Fortran/C/Java). Our approach produces a transparent and flexible process for replication and recomputation of results. Ultimately, its most valuable aspect is the decoupling of methods in computational biology from their implementation. Separating the 'how' (method) of a publication from the 'where' (implementation) promotes genuinely open science and benefits the scientific community as a whole.

q-bio.QM↗

arXiv2018

Dynamics of Insufflated Abdominal Wall Tissue for Magnetically Anchored Surgical Instruments

Magnetically-anchored surgical devices have recently gained attention in abdominal surgery, with the use of magnets to anchor surgical devices onto the insufflated abdominal wall. These anchors have been used to secure passive and active devices, where active device such as robotic manipulators produce motions that would excite the dynamics of the non-rigid abdominal wall. Hence, there is a need to investigate the mechanical dynamics of the abdominal wall tissue in insufflated state, combined with magnetic anchoring, specifically its response to mechanical excitations and the expected disturbances to the operation of the anchored devices. In this paper, loading and unloading tests are performed on a corresponding porcine specimen for dynamics identification. The experiment setup was constructed to emulate the insufflated state of the abdomen with the magnetically anchored mechanism. The tissue responses during unloading are captured and approximated with a general numerical model, which is in turn used for the dynamic analysis of the tissue using Bode plot. The results showed that in such stretched and compressed state, the steady state displacement of the tissue is approximately zero. The maximum transient error was found to be 1mm in displacement using a high magnetic anchoring force. Significant attenuation of the disturbances due to the high stiffness and damping of the abdominal wall, was observed from 100rad/s in the frequency response. If a robotic manipulator was attached to the anchoring device, the typical operating frequency of movements would still produce unattenuated disturbances. It is expected that some error compensation through suitable control strategies is required. These outcomes establish the basis for the controller design and the design specification of the active magnetically-anchored surgical devices for minimal disturbance impact onto the abdominal wall tissue.

physics.med-ph↗