Scale Output Research Articles

Single-Cell Allele-Specific Gene Expression Analysis.

Allele-specific expression is traditionally studied by bulk RNA sequencing, which measures average geneexpression across cells. Single-cell RNA sequencing (scRNA-seq) allows the comparison of expression distribution between the two alleles of a diploid organism, and characterization of allele-specific bursting. Here we describe SCALE, a bioinformatic and statistical framework for allele-specific gene expression analysis by scRNA-seq. SCALE estimates genome-wide bursting kinetics at the allelic level while accounting for technical bias and other complicating factors such as cell size. SCALE detects genes with significantly different bursting kinetics between the two alleles, as well as genes where the two alleles exhibit non-independentbursting processes. Here, we illustrate SCALE on a mouse blastocyst single-cell dataset with step-by-step demonstration from the upstream bioinformatic processing to the downstream biological interpretation of SCALE's output.

Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method

The complexity and heterogeneity of bone tissue require a multiscale modeling to understand its mechanical behavior and its remodeling mechanisms. In this paper, a novel multiscale hierarchical approach including microfibril scale based on hybrid neural network (NN) computation and homogenization equations was developed to link nanoscopic and macroscopic scales to estimate the elastic properties of human cortical bone. The multiscale model is divided into three main phases: (i) in step 0, the elastic constants of collagen-water and mineral-water composites are calculated by averaging the upper and lower Hill bounds; (ii) in step 1, the elastic properties of the collagen microfibril are computed using a trained NN simulation. Finite element calculation is performed at nanoscopic levels to provide a database to train an in-house NN program; and (iii) in steps 2-10 from fibril to continuum cortical bone tissue, homogenization equations are used to perform the computation at the higher scales. The NN outputs (elastic properties of the microfibril) are used as inputs for the homogenization computation to determine the properties of mineralized collagen fibril. The mechanical and geometrical properties of bone constituents (mineral, collagen, and cross-links) as well as the porosity were taken in consideration. This paper aims to predict analytically the effective elastic constants of cortical bone by modeling its elastic response at these different scales, ranging from the nanostructural to mesostructural levels. Our findings of the lowest scale's output were well integrated with the other higher levels and serve as inputs for the next higher scale modeling. Good agreement was obtained between our predicted results and literature data.