Comment instaurer la médecine de précision ? Pour une alliance entre intelligence artificielle et modélisation conceptuelle

Cet article propose des arguments en faveur d’une alliance entre IA et modélisation conceptuelle en vue d’instaurer une médecine de précision. Ses arguments sont illustrés par un cas d’étude concernant la réaction des patients aux anticoagulants. En mobilisant bio-informatique et épistémologie, il développe des éléments de réflexion sur les apports possibles et les limites d’une telle alliance

Initiation of erythropoiesis by BFU-E cells

International audienceErythropoiesis is the process of red blood cell production in the bone marrow. Terminal stages of human erythropoiesis occur in multicellular structures called erythroblastic islands (EBIs). EBIs contain up to several dozen erythroid cells of varying maturities organized around a central macrophage. Immature erythroid cells, burst forming units (BFU-E) circulate in blood and home to bone marrow, where they can have limited but random movement. When BFU-Es approach a macrophage, they divide producing colony forming units-erythroid (CFU-E), which are the next stage of erythroid differentiation. CFU-Es and their immediate progeny, proerythroblasts, can self-renew, differentiate into more mature cells or die by apoptosis. The BFU-E, CFU-E, and the subsequent erythroblast stages provide normal functioning of erythropoiesis. In this work we develop a hybrid discrete-continuous model in order to describe normal erythropoiesis in the bone marrow. Cells are represented as individual objects that move, divide, differentiate, die and interact with each other. We show how BFU-E cells initiate EBIs

Scenario projections for the spread of SARS-CoV-2 Omicron BA.4 and BA.5 subvariants in the US and Texas

This report projects the spread and burden of the highly-transmissible SARS-CoV-2 Omicron BA.4 and BA.5 variants based on data through July 5, 2022. By that date, BA.4 and BA.5 were the predominant variants in the US and COVID-19 hospitalizations were increasing. Using a stochastic compartmental model that tracks population-level immunity derived from infections, primary vaccines, and booster vaccines, we project COVID-19 cases, hospitalizations, and deaths over a twelve month period for both the entire United States and the state of Texas. We simulate sixteen different scenarios in which we vary the transmission properties of the Omicron BA.4/BA.5 variants and the rate of SARS-CoV-2 vaccine booster uptake.Integrative Biolog

COVID-19 Scenario Projections: The Emergence of Omicron in the US

On November 24, 2021, South African scientists announced the rapid spread of a new SARS-CoV-2 variant. Within days, the WHO named the variant Omicron and classified it as a variant of concern (VOC). As of December 15, 2021, many of Omicron's epidemiological characteristics remain uncertain, including its intrinsic transmissibility, ability to evade vaccine-acquired and infection-acquired immunity, and severity. To support situational awareness and planning in the United States, we simulated the emergence and spread of Omicron in the US across a range of plausible scenarios. Using a stochastic compartmental model that tracks population-level immunity against the Delta and Omicron variants derived from infections, primary vaccines, and booster vaccines, we project COVID-19 cases, hospitalizations and deaths over a six month period beginning on December 1, 2021 under 18 different scenarios.Integrative Biolog

COVID-19 Scenario Projections: The Emergence of Omicron in the US - January 2022

As of January 6, 2021, the highly-transmissible SARS-CoV-2 Omicron variant is driving the largest COVID-19 wave in the US to date. The numbers of new cases and hospitalizations continue to rise, straining healthcare systems around the country. On December 16, 2021, we posted projections for the emergence of the Omicron variant under 18 plausible scenarios [1]. At that time, many of Omicron's epidemiological characteristics were uncertain. Recent studies suggest that the Omicron variant is more transmissible, more immune evasive, and less severe than the Delta variant. In this report, we present updated scenario projections that reflect our current understanding of Omicron transmission and severity in the US. Using a stochastic compartmental model that tracks population-level immunity against the Delta and Omicron variants derived from infections, primary vaccines, and booster vaccines, we project COVID-19 cases, hospitalizations, and deaths over a six month period beginning on January 1, 2022 under eight different scenarios.Integrative Biolog

Omicron scenario projections for the Austin-Round Rock MSA

The ongoing COVID-19 surge is straining healthcare systems in the Austin-Round Rock Metropolitan area. As of January 21, 2022, COVID-19 hospital admissions have reached record numbers and the total number of COVID-19 patients in hospitals and ICUs continue to rise. To support response efforts and public risk awareness, we used a data-driven mathematical model to simulate the continued spread of the Omicron variant in the Austin-Round Rock MSA area from January 22, 2022 to June 21, 2022 under four plausible scenarios. Our projections suggest that the 7-day rolling average of reported new cases in the five-county MSA likely peaked on January 9, 2022 at a value 6,109.Integrative Biolog

COVID-19 scenario projections for Austin, Texas - August 2021

To support public health decision-making and healthcare planning, we developed a model for the five-county Austin-Round Rock Metropolitan Statistical Area (henceforth Austin) that can provide real-time estimates of the prevalence and transmission rate of COVID-19 and project healthcare needs into the future. The model incorporates key epidemiological characteristics of the disease, demographic information for Austin, local vaccination estimates, and local mobility data from anonymized cell phone traces. It uses daily COVID-19 hospitalization data to estimate the changing transmission rate and prevalence of the disease. In this report, we use COVID-19 hospitalization data for Austin from March 13, 2020 to July 28, 2021 to estimate the state of the pandemic in the summer of 2021 and project hospitalizations through November of 2021.Integrative Biolog

Mathematical Modeling Reveals That the Administration of EGF Can Promote the Elimination of Lymph Node Metastases by PD-1/PD-L1 Blockade

In the advanced stages of cancers like melanoma, some of the malignant cells leave the primary tumor and infiltrate the neighboring lymph nodes (LNs). The interaction between secondary cancer and the immune response in the lymph node represents a complex process that needs to be fully understood in order to develop more effective immunotherapeutic strategies. In this process, antigen-presenting cells (APCs) approach the tumor and initiate the adaptive immune response for the corresponding antigen. They stimulate the naive CD4+ and CD8+ T lymphocytes which subsequently generate a population of helper and effector cells. On one hand, immune cells can eliminate tumor cells using cell-cell contact and by secreting apoptosis inducing cytokines. They are also able to induce their dormancy. On the other hand, the tumor cells are able to escape the immune surveillance using their immunosuppressive abilities. To study the interplay between tumor progression and the immune response, we develop two new models describing the interaction between cancer and immune cells in the lymph node. The first model consists of partial differential equations (PDEs) describing the populations of the different types of cells. The second one is a hybrid discrete-continuous model integrating the mechanical and biochemical mechanisms that define the tumor-immune interplay in the lymph node. We use the continuous model to determine the conditions of the regimes of tumor-immune interaction in the lymph node. While we use the hybrid model to elucidate the mechanisms that contribute to the development of each regime at the cellular and tissue levels. We study the dynamics of tumor growth in the absence of immune cells. Then, we consider the immune response and we quantify the effects of immunosuppression and local EGF concentration on the fate of the tumor. Numerical simulations of the two models show the existence of three possible outcomes of the tumor-immune interactions in the lymph node that coincide with the main phases of the immunoediting process: tumor elimination, equilibrium, and tumor evasion. Both models predict that the administration of EGF can promote the elimination of the secondary tumor by PD-1/PD-L1 blockade

Living in darkness: Exploring adaptation of Proteus anguinus in 3 dimensions by X-ray imaging

Background: Lightless caves can harbour a wide range of living organisms. Cave animals have evolved a set of morphological, physiological, and behavioural adaptations known as troglomorphisms, enabling their survival in the perpetual darkness, narrow temperature and humidity ranges, and nutrient scarcity of the subterranean environment. In this study, we focused on adaptations of skull shape and sensory systems in the blind cave salamander, Proteus anguinus, also known as olm or simply proteus—the largest cave tetrapod and the only European amphibian living exclusively in subterranean environments. This extraordinary amphibian compensates for the loss of sight by enhanced non-visual sensory systems including mechanoreceptors, electroreceptors, and chemoreceptors. We compared developmental stages of P. anguinus with Ambystoma mexicanum, also known as axolotl, to make an exemplary comparison between cave- and surface-dwelling paedomorphic salamanders. Findings: We used contrast-enhanced X-ray computed microtomography for the 3D segmentation of the soft tissues in the head of P. anguinus and A. mexicanum. Sensory organs were visualized to elucidate how the animal is adapted to living in complete darkness. X-ray microCT datasets were provided along with 3D models for larval, juvenile, and adult specimens, showing the cartilage of the chondrocranium and the position, shape, and size of the brain, eyes, and olfactory epithelium. Conclusions: P. anguinus still keeps some of its secrets. Our high-resolution X-ray microCT scans together with 3D models of the anatomical structures in the head may help to elucidate the nature and origin of the mechanisms behind its adaptations to the subterranean environment, which led to a series of troglomorphisms