Xiaofeng Wang

Jang Ik Cho, Xiaofeng Wang, Yifan Xu et al.

Large sequences of images (or movies) can now be obtained on an unprecedented scale, which poses fundamental challenges to the existing image analysis techniques. The challenges include heterogeneity, (automatic) alignment, multiple comparisons, potential artifacts, and hidden noises. This paper introduces our MATLAB package, Longitudinal Image Sequence Analysis (LISA), as a one-stop ensemble of image processing and analysis tool for comparing a general class of images from either different times, sessions, or subjects. Given two contrasting sequences of images, the image processing in LISA starts with selecting a region of interest in two representative images, followed by automatic or manual segmentation and registration. Automatic segmentation de-noises an image using a mixture of Gaussian distributions of the pixel intensity values, while manual segmentation applies a user-chosen intensity cut-off value to filter out noises. Automatic registration aligns the contrasting images based on a mid-line regression whereas manual registration lines up the images along a reference line formed by two user-selected points. The processed images are then rendered for simultaneous statistical comparisons to generate D, S, T, and P-maps. The D map represents a curated difference of contrasting images, the S map is the non-parametrically smoothed differences, the T map presents the variance-adjusted, smoothed differences, and the P-map provides multiplicity-controlled p-values. These maps reveal the regions with significant differences due to either longitudinal, subject-specific, or treatment changes. A user can skip the image processing step to dive directly into the statistical analysis step if the images have already been processed. Hence, LISA offers flexibility in applying other image pre-processing tools. LISA also has a parallel computing option for high definition images.

Zhe Sun, Ting Wang, Ke Deng et al.

Motivation: Single cell transcriptome sequencing (scRNA-Seq) has become a revolutionary tool to study cellular and molecular processes at single cell resolution. Among existing technologies, the recently developed droplet-based platform enables efficient parallel processing of thousands of single cells with direct counting of transcript copies using Unique Molecular Identifier (UMI). Despite the technology advances, statistical methods and computational tools are still lacking for analyzing droplet-based scRNA-Seq data. Particularly, model-based approaches for clustering large-scale single cell transcriptomic data are still under-explored. Methods: We developed DIMM-SC, a Dirichlet Mixture Model for clustering droplet-based Single Cell transcriptomic data. This approach explicitly models UMI count data from scRNA-Seq experiments and characterizes variations across different cell clusters via a Dirichlet mixture prior. An expectation-maximization algorithm is used for parameter inference. Results: We performed comprehensive simulations to evaluate DIMM-SC and compared it with existing clustering methods such as K-means, CellTree and Seurat. In addition, we analyzed public scRNA-Seq datasets with known cluster labels and in-house scRNA-Seq datasets from a study of systemic sclerosis with prior biological knowledge to benchmark and validate DIMM-SC. Both simulation studies and real data applications demonstrated that overall, DIMM-SC achieves substantially improved clustering accuracy and much lower clustering variability compared to other existing clustering methods. More importantly, as a model-based approach, DIMM-SC is able to quantify the clustering uncertainty for each single cell, facilitating rigorous statistical inference and biological interpretations, which are typically unavailable from existing clustering methods.