FateNet: an integration of dynamical systems and deep learning for cell fate prediction.

Motivation: Understanding cellular decision-making, particularly its timing and impact on the biological system such as tissue health and function, is a fundamental challenge in biology and medicine. Existing methods for inferring fate decisions and cellular state dynamics from single-cell RNA sequencing data lack precision regarding decision points and broader tissue implications. Addressing this gap, we present FateNet, a computational approach integrating dynamical systems theory and deep learning to probe the cell decision-making process using scRNA-seq data.

Fatecode enables cell fate regulator prediction using classification-supervised autoencoder perturbation.

Cell reprogramming, which guides the conversion between cell states, is a promising technology for tissue repair and regeneration, with the ultimate goal of accelerating recovery from diseases or injuries. To accomplish this, regulators must be identified and manipulated to control cell fate. We propose Fatecode, a computational method that predicts cell fate regulators based only on single-cell RNA sequencing (scRNA-seq) data.

Adversarial training improves model interpretability in single-cell RNA-seq analysis.

Motivation: Predictive computational models must be accurate, robust, and interpretable to be considered reliable in important areas such as biology and medicine. A sufficiently robust model should not have its output affected significantly by a slight change in the input. Also, these models should be able to explain how a decision is made to support user trust in the results.

Influence of administration time and sex on natriuretic, diuretic, and kaliuretic effects of diuretics.

Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes.

Understanding the dynamics of SARS-CoV-2 variants of concern in Ontario, Canada: a modeling study.

A year after the initial wild-type Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) strains began their devastation of the world, they were supplanted by new variants of concern (VOC). In Ontario, Canada, the wild type was overtaken first by the Alpha/B1.1.

The mixed blessing of AMPK signaling in Cancer treatments.

Background: Nutrient acquisition and metabolism pathways are altered in cancer cells to meet bioenergetic and biosynthetic demands. A major regulator of cellular metabolism and energy homeostasis, in normal and cancer cells, is AMP-activated protein kinase (AMPK). AMPK influences cell growth via its modulation of the mechanistic target of Rapamycin (mTOR) pathway, specifically, by inhibiting mTOR complex mTORC1, which facilitates cell proliferation, and by activating mTORC2 and cell survival.

Modeling within-Host SARS-CoV-2 Infection Dynamics and Potential Treatments.

The goal of this study was to develop a mathematical model to simulate the actions of drugs that target SARS-CoV-2 virus infection. To accomplish that goal, we have developed a mathematical model that describes the control of a SARS-CoV-2 infection by the innate and adaptive immune components. Invasion of the virus triggers the innate immunity, whereby interferon renders some of the target cells resistant to infection, and infected cells are removed by effector cells.

Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism.

Background: Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of perturbations. In tissues a deficit of these mechanisms is commonly associated with cellular aging and diseases, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as being able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell.

Aging affects circadian clock and metabolism and modulates timing of medication.

Aging is associated with impairments in the circadian rhythms, and with energy deregulation that affects multiple metabolic pathways. The goal of this study is to unravel the complex interactions among aging, metabolism, and the circadian clock. We seek to identify key factors that inform the liver circadian clock of cellular energy status and to reveal the mechanisms by which variations in food intake may disrupt the clock.

Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers During the COVID-19 Pandemic: A Modeling Analysis.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are frequently prescribed for a range of diseases including hypertension, proteinuric chronic kidney disease, and heart failure. There is evidence indicating that these drugs upregulate ACE2, a key component of the renin-angiotensin system (RAS) and is found on the cells of a number of tissues, including the epithelial cells in the lungs. While ACE2 has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease, it also serves as a receptor for both SARS-CoV and SARS-CoV-2 via binding with the spike protein of the virus, thereby allowing it entry into host cells.

Network centrality analysis of eye-gaze data in autism spectrum disorder.

Individuals suffering from autism spectrum disorder (ASD) exhibit impaired social communication, the manifestations of which include abnormal eye contact and gaze. In this study, we first seek to characterize the spatial and temporal attributes of this atypical eye gaze. To achieve that goal, we analyze and compare eye-tracking data of ASD and typical development (TD) children.