Statistical modeling of cell‐to‐cell variability in viral infection during passaging in suspension cell culture: Application in Monte‐Carlo simulation

Saxena, Abha; Suryateja, Ravutla; Upadhyay, Vikas; Jana, Soumya; Murhammer, David W.; Giri, Lopamudra

doi:10.1002/bit.27295

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…PDF fitting using MLE : Statistical analysis of the Ca 2+ ‐signatures of each cell was also performed by the fitting of probability density functions (PDFs) using maximum Loglikelihood (

LL

) estimation (Saxena et al, 2020)

LL = {false\sum}_{i = 1}^{n} f_{i} (x_{i}| θ),

where

x_{i}

are

{([], {Ca}^{2 +})}_{s}

time series and

θ

are the parameters of distribution). Fitting was performed for six distributions: normal, exponential, gamma, Birnbaum–Saunders (BS), and generalized extreme value distribution (Table S2).…”

Section: Methodsmentioning

confidence: 99%

“…Fitting was performed for six distributions: normal, exponential, gamma, Birnbaum–Saunders (BS), and generalized extreme value distribution (Table S2). The distribution that yielded the minimum Akaike information criterion (

AIC = - (2 \times Loglikelihood) + (2 \times number of parameters)

) was considered to be the best fit (Saxena et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…PDF fitting using MLE: Statistical analysis of the Ca 2+ -signatures of each cell was also performed by the fitting of probability density functions (PDFs) using maximum Loglikelihood (LL) estimation (Saxena et al, 2020…”

Section: Feature Extractionmentioning

confidence: 99%

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A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

Dhyani,

George,

Gare

et al. 2023

Hippocampus

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Calcium (Ca2+) imaging reveals a variety of correlated firing in cultures of dissociated hippocampal neurons, pinpointing the non‐synaptic paracrine release of glutamate as a possible mediator for such firing patterns, although the biophysical underpinnings remain unknown. An intriguing possibility is that extracellular glutamate could bind metabotropic receptors linked with inositol trisphosphate (IP3) mediated release of Ca2+ from the endoplasmic reticulum of individual neurons, thereby modulating neural activity in combination with sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA) and voltage‐gated Ca2+ channels (VGCC). However, the possibility that such release may occur in different neuronal compartments and can be inherently stochastic poses challenges in the characterization of such interplay between various Ca2+ channels. Here we deploy biophysical modeling in association with Monte Carlo parameter sampling to characterize such interplay and successfully predict experimentally observed Ca2+ patterns. The results show that the neurotransmitter level at the plasma membrane is the extrinsic source of heterogeneity in somatic Ca2+ transients. Our analysis, in particular, identifies the origin of such heterogeneity to an intrinsic differentiation of hippocampal neurons in terms of multiple cellular properties pertaining to intracellular Ca2+ signaling, such as VGCC, IP3 receptor, and SERCA expression. In the future, the biophysical model and parameter estimation approach used in this study can be upgraded to predict the response of a system of interconnected neurons.

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“…PDF fitting using MLE : Statistical analysis of the Ca 2+ ‐signatures of each cell was also performed by the fitting of probability density functions (PDFs) using maximum Loglikelihood (

LL

) estimation (Saxena et al, 2020)

LL = {false\sum}_{i = 1}^{n} f_{i} (x_{i}| θ),

where

x_{i}

are

{([], {Ca}^{2 +})}_{s}

time series and

θ

are the parameters of distribution). Fitting was performed for six distributions: normal, exponential, gamma, Birnbaum–Saunders (BS), and generalized extreme value distribution (Table S2).…”

Section: Methodsmentioning

confidence: 99%

AIC = - (2 \times Loglikelihood) + (2 \times number of parameters)

) was considered to be the best fit (Saxena et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

Dhyani,

George,

Gare

et al. 2023

Hippocampus

Self Cite

View full text Add to dashboard Cite

show abstract

“…Meta-data analysis refers to the statistical analysis of the data from independent primary studies that address the same research question, and aims to generate a quantitative estimate of the studied phenomenon [22]. We used Monte-Carlo simulations [23] to conduct a meta-data analysis to compare the micronutrient absorption rate among the control and ONS group. Monte Carlo simulation is used to generate a set of random numbers according to the data distribution (normal and others) and parameters for each variable data (Please refer to the supplementary materials for the details).…”

Section: Meta-data Analysismentioning

confidence: 99%

Effect of oral nutrition supplement on growth in preschool children – a systems physiology-based in silico analysis

Nishanthi¹,

Chheda²,

Gurumaani³

et al. 2024

Indian J Child Health

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Introduction: Optimum nutrition is the cornerstone of child growth and development. Childhood is a period of rapid growth and development. Children of preschool age have higher nutritional needs and are often at risk of nutrient deficiencies. Objective: The present study was designed to evaluate the effect of an oral nutritional supplement (ONS) on growth parameters in a representative population. Methods: We used the systems-biology-based mathematical model for child growth to analyze the effect of ONS on growth in a representative in silico population of preschool children. The analysis included changes in average growth velocities of weight, height, muscle mass, fat mass, fat-free mass, and bone mass. We used meta-data analysis for evaluating the absorption of micronutrients present in the ONS that affects growth in preschool children. Results: The results of the analysis showed one serving of ONS in milk/day improved the weight gain velocity by 1.7 times in preschool children. The linear growth was 1.04 times higher than the control. The absorption of micronutrients such as iron, vitamin K, calcium, and magnesium was higher in the ONS group. Conclusions: This study indicates that the ONS containing macro and micronutrients, docosahexaenoic acid (DHA), and prebiotics can potentiate growth and development in preschool children. It provides micronutrients that can be readily absorbed which are essential for other vital functions in the body.

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Mapping of structural arrangement of cells and collective calcium transients: an integrated framework combining live cell imaging using confocal microscopy and UMAP-assisted HDBSCAN-based approach

Gare

Chel

Abhinav

et al. 2022

Integrative Biology

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Live cell calcium (Ca2+) imaging is one of the important tools to record cellular activity during in vitro and in vivo preclinical studies. Specially, high-resolution microscopy can provide valuable dynamic information at the single cell level. One of the major challenges in the implementation of such imaging schemes is to extract quantitative information in the presence of significant heterogeneity in Ca2+ responses attained due to variation in structural arrangement and drug distribution. To fill this gap, we propose time-lapse imaging using spinning disk confocal microscopy and machine learning-enabled framework for automated grouping of Ca2+ spiking patterns. Time series analysis is performed to correlate the drug induced cellular responses to self-assembly pattern present in multicellular systems. The framework is designed to reduce the large-scale dynamic responses using uniform manifold approximation and projection (UMAP). In particular, we propose the suitability of hierarchical DBSCAN (HDBSCAN) in view of reduced number of hyperparameters. We find UMAP-assisted HDBSCAN outperforms existing approaches in terms of clustering accuracy in segregation of Ca2+ spiking patterns. One of the novelties includes the application of non-linear dimension reduction in segregation of the Ca2+ transients with statistical similarity. The proposed pipeline for automation was also proved to be a reproducible and fast method with minimal user input. The algorithm was used to quantify the effect of cellular arrangement and stimulus level on collective Ca2+ responses induced by GPCR targeting drug. The analysis revealed a significant increase in subpopulation containing sustained oscillation corresponding to higher packing density. In contrast to traditional measurement of rise time and decay ratio from Ca2+ transients, the proposed pipeline was used to classify the complex patterns with longer duration and cluster-wise model fitting. The two-step process has a potential implication in deciphering biophysical mechanisms underlying the Ca2+ oscillations in context of structural arrangement between cells.

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Statistical modeling of cell‐to‐cell variability in viral infection during passaging in suspension cell culture: Application in Monte‐Carlo simulation

Cited by 3 publications

References 45 publications

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

Effect of oral nutrition supplement on growth in preschool children – a systems physiology-based in silico analysis

Mapping of structural arrangement of cells and collective calcium transients: an integrated framework combining live cell imaging using confocal microscopy and UMAP-assisted HDBSCAN-based approach

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