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Reichner, J. S.

Publications and source records attributed to Reichner, J. S..

2 recordsLinked to original sources

Generative modeling of biological shapes and images using a probabilistic α-shape sampler

Understanding morphological variation is an important task in many areas of computational biology. Recent studies have focused on developing computational tools for the task of sub-image selection which aims at identifying structural features that best describe the variation between classes of shapes. A major part in assessing the utility of these approaches is to demonstrate their performance on both simulated and real datasets. However, when creating a model for shape statistics, real data can be difficult to access and the sample sizes for these data are often small due to them being expensive to collect. Meanwhile, the current landscape of generative models for shapes has been mostly limited to approaches that use black-box inference--making it difficult to systematically assess the power and calibration of sub-image models. In this paper, we introduce the -shape sampler: a probabilistic framework for generating realistic 2D and 3D shapes based on probability distributions which can be learned from real data. We demonstrate our framework using proof-of-concept examples and in two real applications in biology where we generate (i) 2D images of healthy and septic neutrophils and (ii) 3D computed tomography (CT) scans of primate mandibular molars. The -shape sampler R package is open-source and can be downloaded at https://github.com/lcrawlab/ashapesampler. Author SummaryUsing shapes and images to understand genotypic and phenotypic variation has proven to be an effective strategy in many biological applications. Unfortunately, shape data can be expensive to collect and, as a result, sample sizes for analyses are often small. Despite methodological advancements in shape statistics and machine learning, benchmarking standards for evaluating new computational tools via data simulation is still underdeveloped. In this paper, we present a probability-based pipeline called the -shape sampler which has the flexibility to generate new and unobserved shapes based on an input set of data. We extensively evaluate the generative capabilities of our pipeline using 2D cellular images of neutrophils and 3D mandibular molars from two different suborders of primates.

bioinformatics↗

Context-dependent role of vinculin in neutrophil adhesion, motility and trafficking

Neutrophils are innate immune effector cells that traffic from the peripheral blood to extravascular sites of inflammation. {beta}2 integrins are involved during multiple phases of neutrophil recruitment, including the transition from rolling to arrest, firm attachment and motility within the vasculature. Following neutrophil arrest, adhesion stabilization occurs as the neutrophil interacts with the endothelial surface and crawls into a favorable position for extravasation. The cytoskeletal protein vinculin has been implicated in other cell types as a regulator of adhesion strength by promoting focal adhesion maturation and as a sensor of the mechanical properties of the microenvironment. Neutrophils express vinculin but do not form mature focal adhesions. Here, we characterize the role of vinculin in {beta}2 integrin-dependent neutrophil adhesion, motility, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. In the presence of forces from fluid flow, vinculin was not required for neutrophil adhesion or migration. Vinculin deficiency only mildly attenuated neutrophil traction stresses and spreading on stiff, but not soft, polyacrylamide gels indicating a minor role for vinculin in the mechanosensing of the neutrophil as compared to slower moving mesenchymal cells that form mature focal adhesions. Consistent with these findings, we observe in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for neutrophil recruitment and motility in vivo.

immunology↗