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Register a new userIntegrated Biophysical Modeling and Image Analysis: Application to Neuro-Oncology
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Central nervous system (CNS) tumors come with the vastly heterogeneous histologic, molecular and radiographic landscape, rendering their precise characterization challenging. The rapidly growing fields of biophysical modeling and radiomics have shown promise in better characterizing the molecular, spatial, and temporal heterogeneity of tumors. Integrative analysis of CNS tumors, including clinically-acquired multi-parametric magnetic resonance imaging (mpMRI) and the inverse problem of calibrating biophysical models to mpMRI data, assists in identifying macroscopic quantifiable tumor patterns of invasion and proliferation, potentially leading to improved (i) detection/segmentation of tumor sub-regions, and (ii) computer-aided diagnostic/prognostic/predictive modeling. This paper presents a summary of (i) biophysical growth modeling and simulation, (ii) inverse problems for model calibration, (iii) their integration with imaging workflows, and (iv) their application on clinically-relevant studies. We anticipate that such quantitative integrative analysis may even be beneficial in a future revision of the World Health Organization (WHO) classification for CNS tumors, ultimately improving patient survival prospects.
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ANDy , Activity Networks with Delays, is a discrete time framework aimed at the qualitative modelling of time-dependent activities. The modular and concise syntax makes ANDy suitable for an easy and natural modelling of time-dependent biological systems (i.e., regulatory pathways). Activities involve entities playing the role of activators, inhibitors or products of biochemical network operation. Activities may have given duration, i.e., the time required to obtain results. An entity may represent an object (e.g., an agent, a biochemical species or a family of thereof) with a local attribute, a state denoting its level (e.g., concentration, strength). Entities levels may change as a result of an activity or may decay gradually as time passes by. The semantics of ANDy is formally given via high-level Petri nets ensuring this way some modularity. As main results we show that ANDy systems have finite state representations even for potentially infinite processes and it well adapts to the modelling of toxic behaviours. As an illustration, we present a classification of toxicity properties and give some hints on how they can be verified with existing tools on ANDy systems. A small case study on blood glucose regulation is provided to exemplify the ANDy framework and the toxicity properties.
{mu}Manager, an open-source microscopy acquisition software, has been an essential tool for many microscopy experiments over the past 15 years, but is not easy to use for experiments in which image acquisition and analysis are closely coupled. This is because {mu}Manager libraries are written in C++ and Java, whereas image processing is increasingly carried out with data science and machine learning tools most easily accessible through the Python programming language. We present Pycro-Manager, a tool that enables rapid development of such experiments, while also providing access to the wealth of existing tools within {mu}Manager through Python.
The focus of pancreatic cancer research has been shifted from pancreatic cancer cells towards their microenvironment, involving pancreatic stellate cells that interact with cancer cells and influence tumor progression. To quantitatively understand the pancreatic cancer microenvironment, we construct a computational model for intracellular signaling networks of cancer cells and stellate cells as well as their intercellular communication. We extend the rule-based BioNetGen language to depict intra- and inter-cellular dynamics using discrete and continuous variables respectively. Our framework also enables a statistical model checking procedure for analyzing the system behavior in response to various perturbations. The results demonstrate the predictive power of our model by identifying important system properties that are consistent with existing experimental observations. We also obtain interesting insights into the development of novel therapeutic strategies for pancreatic cancer.
Data analysis pipelines are known to be impacted by computational conditions, presumably due to the creation and propagation of numerical errors. While this process could play a major role in the current reproducibility crisis, the precise causes of such instabilities and the path along which they propagate in pipelines are unclear. We present Spot, a tool to identify which processes in a pipeline create numerical differences when executed in different computational conditions. Spot leverages system-call interception through ReproZip to reconstruct and compare provenance graphs without pipeline instrumentation. By applying Spot to the structural pre-processing pipelines of the Human Connectome Project, we found that linear and non-linear registration are the cause of most numerical instabilities in these pipelines, which confirms previous findings.
A resource selection function is a model of the likelihood that an available spatial unit will be used by an animal, given its resource value. But how do we appropriately define availability? Step-selection analysis deals with this problem at the scale of the observed positional data, by matching each used step (connecting two consecutive observed positions of the animal) with a set of available steps randomly sampled from a distribution of observed steps or their characteristics. Here we present a simple extension to this approach, termed integrated step-selection analysis (iSSA), which relaxes the implicit assumption that observed movement attributes (i.e. velocities and their temporal autocorrelations) are independent of resource selection. Instead, iSSA relies on simultaneously estimating movement and resource-selection parameters, thus allowing simple likelihood-based inference of resource selection within a mechanistic movement model. We provide theoretical underpinning of iSSA, as well as practical guidelines to its implementation. Using computer simulations, we evaluate the inferential and predictive capacity of iSSA compared to currently used methods. Our work demonstrates the utility of iSSA as a general, flexible and user-friendly approach for both evaluating a variety of ecological hypotheses, and predicting future ecological patterns.
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