Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of colonoscopies are unknown. We aimed to determine an schedule for US population its dependencies on objective (life years gained or incidence, mortality, cost reduction) setting in which is performed. used our established open-source microsimulation model CMOST calculate optimized colonoscopy schedules with one, two, three four between 20 90 age. A single was...

ABSTRACT Innumerable variants of the susceptible-exposed-infected-recovered (SEIR) model predicted course COVID-19 infections for different countries, along with ‘peaks’ and subsequent decline infections. One thing these models could not have prospectively in January or did adapt to following months is that peak rather a ‘plateau’ many countries. For example, USA UK been persisting at same high approximately 30,000 5,000 daily new respectively, more than month. Other countries had shorter...

Abstract Current epidemiological models can in principle model the temporal evolution of a pandemic. However, any such will rely on parameters that are unknown, which practice estimated using stochastic and poorly measured quantities. As result, an early prediction long-term pandemic quickly lose relevance, while late be too to useful for disaster management. Unless is designed adaptive, it bound either relevance over time, or trust thus not have second-chance retraining. We propose strategy...

A quantitative COVID-19 model that incorporates hidden asymptomatic patients is developed, and an analytic solution in parametric form given. The the impact of lock-down resulting spatial migration population due to announcement lock-down. method presented for estimating parameters from real-world data, it shown various phases observed epidemiological data are captured well. It increase infections slows down herd immunity achieved when active symptomatic 10-25% four countries we studied....

Abstract A person clinically diagnosed with COVID 19 can infect others for several days before and after the onset of symptoms. At epidemiological level, this information on how infectious someone is lies embedded implicitly in serial interval data. Other clinical indicators infectiousness based temporal kinetics viral shedding from nasopharyngeal swabs sputum show former decaying weeks sooner than latter. In work, we attempt to provide a better quantitative estimate profile using data...

Protein structure and function can be severely altered by even a single amino acid mutation. Predictions of mutational effects using extensive artificial intelligence (AI)-based models, although accurate, remain as enigmatic the experimental observations in terms improving intuitions about contributions various factors. Inspired Lipinski's rules for drug-likeness, we devise simple thresholding criteria on five different descriptors such conservation, which have so far been limited to...

Amino acid mutations in proteins are random and those which beneficial or neutral survive during the course of evolution. Conservation co-evolution analyses performed on multiple sequence alignment homologous to understand how important different amino acids groups them are. However, these traditional do not explore directed influence mutations, such as compensatory effects. In this work we develop a method capture evolutionary impact one all other acids, provide visual network...

Performing a complete deep mutational scan with all single point mutations may not be practical, and even required, especially if predictive computational models can developed. Computational are however naive to cellular response in the myriads of assay-conditions. In realistic paradigm assay context-aware hybrid that combine minimal experimental data from scans structure, sequence information models, we define evaluate different strategies for choosing this set. We evaluated trivial...

Abstract At the sequence level it is hard to describe complexity of viruses which allows them challenge host immune system, some for a few weeks and others up complete compromise. Paradoxically, viral genomes are both complex simple. Complex because amino acid mutation rates very high, yet remain functional. Simple they have barely around 10 types proteins, so protein-protein interaction networks not insightful. In this work we use fine-grained information their evolutionary characteristics...

Acinetobacter baumannii, has been developing resistance to even the last line of drugs. Antimicrobial peptides (AMPs) which bacteria do not develop easily may be hope. A few independent experimental studies have designed and studied activity AMPs on A. however number such are still limited. With goal a rational approach screening against we carefully curated drug data from 75 cationic AMPs, all measured with similar protocol, same ATCC 19606 strain. quantitative model developed validated...

Summary The role of complete lockdowns in reducing the reproduction ratios (R t ) COVID-19 is now established. However, persisting reality many countries no longer a lockdown, but restrictions varying degrees using different choices Non-pharmaceutical interaction (NPI) policies. A scientific basis for understanding effectiveness these graded NPI policies R urgently needed to address concerns on personal liberties and economic activities. In this work, we develop systematic relation between...

The development of drug resistance by bacterial adaptation or undesirable damage to gut microbiota raise new challenges in design and require one look beyond the canonical approach screening multiple drugs against a single target. We develop complementary approach, targets, quantitatively illustrate it for specific case antibiotic targeting membranes. curated data on activity daptomycin Staphylococcus aureus strains with different membrane compositions, varying mainly lysylation validated...

Unconventional protein secretion (UPS) is an important phenomenon with fundamental implications to cargo export. How eukaryotic proteins transported by UPS are recognized without a conventional signal peptide has been open question. It was recently observed that diacidic amino acid motif (ASP-GLU or DE) necessary for the of superoxide dismutase 1 (SOD1) from yeast under nutrient starvation. Taking cue this discovery, we explore hypothesis whether DE, which can occur fairly ubiquitously,...

Abstract Several questions resonate as the governments relax their COVID-19 mitigation policies - is it too early to them, were effective they could have been. Answering these about past or crafting newer policy decisions in future requires a quantification of how choices affect spread infection. Policy landscape well infection trajectories from different states and countries diverged so fast that comparing learning them has not been easy. In this work, we standardize pool together ensemble...

Background: By mid-September of 2020, the number daily new infections in India have crossed 95,000. To facilitate an intuition for spatio-temporal development pandemic and to help resource deployment planning, we analyze describe how disease burden almost-predictably shifted from large metropolitan districts sub-urban districts. Methods: We gathered publicly available granular data 186 different (equivalent counties) on their COVID-19 deaths during 15 April 31 August 2020 period. These...

ABSTRACT BACKGROUND When the lockdowns are relaxed, responsibility of mitigating COVID-19 spread shifts from governments to individuals. To know how conduct one-self, it is important for everyone risks transmission during quotidian activities - meetings, meals, etc, individuals who known them and looking healthy. METHODS The detailed case-studies corresponding 425 infections upon point-exposures over a specified duration curated. data case studies summarized reorganized reflect different...

Abstract Several questions resonate as the governments relax their COVID-19 mitigation policies - is it too early to them, were effective they could have been. Answering these about past or crafting newer policy decisions in future requires a quantification of how choices affect spread infection. Policy landscape well infection trajectories from different states and countries diverged so fast that comparing learning them has not been easy. In this work, we standardize pool together ensemble...

Abstract Bacterial swimming alternates between straight runs for several seconds and tumbles into random directions. Chemotactic bacteria remember nutrient sensing history, change tumble frequency to move toward nutrients. A question that has not been addressed is the significance of nutrition gain multiplication bacterial population with chemotaxis mechanism. To quantify these effects, we introduce a microsimulation model, which seamlessly integrates detailed observations assumptions about...

ABSTRACT Viruses are simultaneously simple and complex. Simple because they have barely around ten types of proteins compared to tens thousands in bacteria. Complex amino acid mutation rates very high, challenging host immune system drugs. In this work we use the co-evolution acids network characteristics that arise out it describe complexity hidden multitude variations a viral genome. Using large-scale genomic data, several viruses was compared. Interestingly, co-evolutionary relations were...

Abstract The peak of the daily new infections in COVID-19 remained qualitative description and elusive arrival. Because lack clarity what to expect from peak, apart hope that one day will be reached, there has been no metric describe success implemented strategies. We propose a way predicting number can expected after lockdown, assuming they come asymptomatic cases prior lockdown using linear response theory. These predictions for several western countries faithfully follow observed weeks...

Abstract Mutational effects predictions continue to improve in accuracy as advanced artificial intelligence (AI) algorithms are trained on exhaustive experimental data. The next natural questions ask if it is now possible gain insights into which attribute of the mutation contributes how much mutational effects, and one can develop universal rules for mapping descriptors effects. In this work, we mainly address former aspect using a framework interpretable AI. Relations between...

Background By mid-September of 2020, the number daily new infections in India crossed 95,000. We aimed to characterize spatio-temporal shifts disease burden as rose during first wave COVID-19. Methods gathered publicly available district-level (equivalent counties) granular data for 15 April 31 August 2020 period. used epidemiological from 186 districts with highest case 31, 559,566 active cases and 2,715,656 cumulative infections, governing epidemic parameters were estimated by fitting it a...

A bacterial chemotaxis mechanism is activated when nutrients bind to surface receptors. The sequence of intra- and interprotein events in this signal cascade from the receptors eventual molecular motors has been clearly identified. However, atomistic details remain elusive, as general may be expected intraprotein transduction pathways, especially fibrillar proteins are involved. We performed calculations methyl accepting chemoprotein (MCP)–CheA–CheW multidomain complex Escherichia coli,...

Abstract How does one interpret the observed increase or decrease in COVID-19 case rates? Did compliance to non-pharmaceutical interventions, seasonal changes temperature influence transmission rates are they purely an artefact of number tests? To answer these questions, we estimate effect-sizes from different factors on reproduction ratios (R t ) states USA during March 9 August 9. Ideally R should be less than 1 keep pandemic under control and our model predicts many contributed...