•We model the effectiveness of COVID vaccine strategies in India using a SEIR model.•Regardless of efficacy, prioritized vaccination of >60 years olds leads to greater reductions in deaths than ...prioritized vaccination of other age groups.•Prioritized vaccination of younger adults (20–40 years) often reduced symptomatic infections most significantly.•Increased speed of rollout of COVID-19 vaccine reduced the relative differences between different vaccine allocation strategies.•Vaccination along with non-pharmaceutical measures of disease control offers the best chance in curbing the duration of this outbreak.
The development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions.
We used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations.
Prioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination.
Our findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.
Chromosomes within eukaryotic cell nuclei at interphase are not positioned at random, since gene-rich chromosomes are predominantly found towards the interior of the cell nucleus across a number of ...cell types. The physical mechanisms that could drive and maintain the spatial segregation of chromosomes based on gene density are unknown. Here, we identify a mechanism for such segregation, showing that the territorial organization of chromosomes, another central feature of nuclear organization, emerges naturally from our model. Our computer simulations indicate that gene density-dependent radial segregation of chromosomes arises as a robust consequence of differences in non-equilibrium activity across chromosomes. Arguing that such differences originate in the inhomogeneous distribution of ATP-dependent chromatin remodeling and transcription machinery on each chromosome, we show that a variety of non-random positional distributions emerge through the interplay of such activity, nuclear shape and specific interactions of chromosomes with the nuclear envelope. Results from our model are in reasonable agreement with experimental data and we make a number of predictions that can be tested in experiments.
Optimizing testing for COVID-19 in India Cherian, Philip; Krishna, Sandeep; Menon, Gautam I
PLoS computational biology,
07/2021, Letnik:
17, Številka:
7
Journal Article
Recenzirano
Odprti dostop
COVID-19 testing across India uses a mix of two types of tests. Rapid Antigen Tests (RATs) are relatively inexpensive point-of-care lateral-flow-assay tests, but they are also less sensitive. The ...reverse-transcriptase polymerase-chain-reaction (RT-PCR) test has close to 100% sensitivity and specificity in a laboratory setting, but delays in returning results, as well as increased costs relative to RATs, may vitiate this advantage. India-wide, about 49% of COVID-19 tests are RATs, but some Indian states, including the large states of Uttar Pradesh (pop. 227.9 million) and Bihar (pop. 121.3 million) use a much higher proportion of such tests. Here we show, using simulations based on epidemiological network models, that the judicious use of RATs can yield epidemiological outcomes comparable to those obtained through RT-PCR-based testing and isolation of positives, provided a few conditions are met. These are (a) that RAT test sensitivity is not too low, (b) that a reasonably large fraction of the population, of order 0.5% per day, can be tested, (c) that those testing positive are isolated for a sufficient duration, and that (d) testing is accompanied by other non-pharmaceutical interventions for increased effectiveness. We assess optimal testing regimes, taking into account test sensitivity and specificity, background seroprevalence and current test pricing. We find, surprisingly, that even 100% RAT test regimes should be acceptable, from both an epidemiological as well as a economic standpoint, provided the conditions outlined above are met.
Modelling the first wave of COVID-19 in India Hazra, Dhiraj Kumar; Pujari, Bhalchandra S; Shekatkar, Snehal M ...
PLoS computational biology,
10/2022, Letnik:
18, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Estimating the burden of COVID-19 in India is difficult because the extent to which cases and deaths have been undercounted is hard to assess. Here, we use a 9-component, age-stratified, ...contact-structured epidemiological compartmental model, which we call the INDSCI-SIM model, to analyse the first wave of COVID-19 spread in India. We use INDSCI-SIM, together with Bayesian methods, to obtain optimal fits to daily reported cases and deaths across the span of the first wave of the Indian pandemic, over the period Jan 30, 2020 to Feb 15, 2021. We account for lock-downs and other non-pharmaceutical interventions (NPIs), an overall increase in testing as a function of time, the under-counting of cases and deaths, and a range of age-specific infection-fatality ratios. We first use our model to describe data from all individual districts of the state of Karnataka, benchmarking our calculations using data from serological surveys. We then extend this approach to aggregated data for Karnataka state. We model the progress of the pandemic across the cities of Delhi, Mumbai, Pune, Bengaluru and Chennai, and then for India as a whole. We estimate that deaths were undercounted by a factor between 2 and 5 across the span of the first wave, converging on 2.2 as a representative multiplier that accounts for the urban-rural gradient. We also estimate an overall under-counting of cases by a factor of between 20 and 25 towards the end of the first wave. Our estimates of the infection fatality ratio (IFR) are in the range 0.05—0.15, broadly consistent with previous estimates but substantially lower than values that have been estimated for other LMIC countries. We find that approximately 35% of India had been infected overall by the end of the first wave, results broadly consistent with those from serosurveys. These results contribute to the understanding of the long-term trajectory of COVID-19 in India.
Cells in microbial colonies integrate information across multiple spatial and temporal scales while sensing environmental cues. A number of photosynthetic cyanobacteria respond in a directional ...manner to incident light, resulting in the phototaxis of individual cells. Colonies of such bacteria exhibit large-scale changes in morphology, arising from cell-cell interactions, during phototaxis. These interactions occur through type IV pili-mediated physical contacts between cells, as well as through the secretion of complex polysaccharides ('slime') that facilitates cell motion. Here, we describe a computational model for such collective behaviour in colonies of the cyanobacterium Synechocystis. The model is designed to replicate observations from recent experiments on the emergent response of the colonies to varied light regimes. It predicts the complex colony morphologies that arise as a result. We ask if changes in colony morphology during phototaxis can be used to infer if cells integrate information from multiple light sources simultaneously, or respond to these light sources separately at each instant of time. We find that these two scenarios cannot be distinguished from the shapes of colonies alone. However, we show that tracking the trajectories of individual cyanobacteria provides a way of determining their mode of response. Our model allows us to address the emergent nature of this class of collective bacterial motion, linking individual cell response to the dynamics of colony shape.
Stem cells integrate signals from the microenvironment to generate lineage-specific gene expression programs upon differentiation. Undifferentiated cell nuclei are easily deformable, with an active ...transcriptome, whereas differentiated cells have stiffer nuclei and condensed chromatin. Chromatin organization in the stem cell state is known to be highly dynamic but quantitative characterizations of its plasticity are lacking. Using fluorescence imaging, we study the spatio-temporal dynamics of nuclear architecture and chromatin compaction in mouse embryonic stem (ES) cells and differentiated states. Individual ES cells exhibit a relatively narrow variation in chromatin compaction, whereas primary mouse embryonic fibroblasts (PMEF) show broad distributions. However, spatial correlations in chromatin compaction exhibit an emergent length scale in PMEFs, although they are unstructured and longer ranged in ES cells. We provide evidence for correlated fluctuations with large amplitude and long intrinsic timescales, including an oscillatory component, in both chromatin compaction and nuclear area in ES cells. Such fluctuations are largely frozen in PMEF. The role of actin and Lamin A/C in modulating these fluctuations is described. A simple theoretical formulation reproduces the observed dynamics. Our results suggest that, in addition to nuclear plasticity, correlated spatio-temporal structural fluctuations of chromatin in undifferentiated cells characterize the stem cell state.
Recent measurements of the distribution of end-to-end distance in short DNA molecules infer cooperative stretching fluctuations. The assumptions underlying the analysis can be questioned if ...transient, thermally induced defects producing a localized decrease in bending stiffness are present in thermal equilibrium, such as regions in which DNA melts locally (bubbles), sustains large-angle bends (kinks), or can locally transform into an alternative (S-DNA) state. We study a generalized discrete worm-like chain model for DNA, capable of describing these experiments, showing that the model yields accurate fits to available experimental data. Our results indicate that DNA bending arising from such localized defects, rather than solely stretching, can be an equal contributor to end-to-end distance fluctuations for 35-bp DNA and contributes nontrivially to such fluctuations at all scales below the persistence length. The analysis suggests that such fluctuations should exhibit a scale-dependent cooperativity, specifically relevant in determining the behavior of short chains, but which saturates rapidly to a length-independent value for longer DNA, to ensure a consistent physical description of DNA across multiple scales. Our approach provides a minimal, yet accurate, coarse-grained description of DNA at the subpersistence length scales of current experimental interest.
Cyanobacteria are a diverse group of photosynthetic bacteria that exhibit phototaxis, or motion in response to light. Cyanobacteria such as Synechocystis sp. secrete a mixture of complex ...polysaccharides that facilitate cell motion, while their type 4 pili allow them to physically attach to each other. Even though cells can respond individually to light, colonies are observed to move collectively towards the light source in dense finger-like projections. We present an agent-based model for cyanobacterial phototaxis that accounts for slime deposition as well as for direct physical links between bacteria, mediated through their type 4 pili. We reproduce the experimentally observed aggregation of cells at the colony boundary as a precursor to finger formation. Our model also describes the changes in colony morphology that occur when the location of the light source is abruptly changed. We find that the overall motion of cells toward light remains relatively unimpaired even if a fraction of them do not sense light, allowing heterogeneous populations to continue to mount a robust collective response to stimuli. Our work suggests that in addition to bio-chemical signalling via diffusible molecules in the context of bacterial quorum-sensing, short-ranged physical interactions may also contribute to collective effects in bacterial motility.
Cyanobacteria rely on photosynthesis, and thus have evolved complex responses to light. These include phototaxis, the ability of cells to sense light direction and move towards or away from it. ...Analysis of mutants has demonstrated that phototaxis requires the coordination of multiple photoreceptors and signal transduction networks. The output of these networks is relayed to type IV pili (T4P) that attach to and exert forces on surfaces or other neighboring cells to drive "twitching" or "gliding" motility. This, along with the extrusion of polysaccharides or "slime" by cells, facilitates the emergence of group behavior. We evaluate recent models that describe the emergence of collective colony-scale behavior from the responses of individual, interacting cells. We highlight the advantages of "active matter" approaches in the study of bacterial communities, discussing key differences between emergent behavior in cyanobacterial phototaxis and similar behavior in chemotaxis or quorum sensing.
When embryonic stem cells differentiate, the mechanical properties of their nuclei evolve en route to their terminal state. Measurements of the deformability of cell nuclei in the transitional state ...that intervenes between the embryonic stem-cell state and the differentiation primed state of mouse stem cells indicate that such nuclei are auxetic; i.e., they have a negative Poisson’s ratio. We show, using a theoretical model, how this remarkable mechanical behavior results from the coupling between chromatin compaction states and nuclear shape. Our biophysical approach, which treats chromatin as an active polymer system whose mechanics is modulated by nucleosome binding and unbinding, reproduces experimental results. It provides testable predictions for changes in chromatin compaction as a function of applied force, for the correlations of chromatin compaction and nuclear shape, and for the in-phase and out-of-phase response of these quantities to an applied uniaxial oscillatory force. Our model yields a biophysical interpretation of the epigenetic landscape of stem cells, also suggesting how this landscape might be probed experimentally.
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