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Henderson, D. A.

Publications and source records attributed to Henderson, D. A..

2 recordsLinked to original sources

Insitutype: likelihood-based cell typing for single cell spatial transcriptomics

Accurate cell typing is fundamental to analysis of spatial single-cell transcriptomics, but legacy scRNA-seq algorithms can underperform in this new type of data. We have developed a cell typing algorithm, Insitutype, designed for statistical and computational efficiency in spatial transcriptomics data. Insitutype is based on a likelihood model that weighs the evidence from every expression value, extracting all the information available in each cells expression profile. This likelihood model underlies a Bayes classifier for supervised cell typing, and an Expectation-Maximization algorithm for unsupervised and semi-supervised clustering. Insitutype also leverages alternative data types collected in spatial studies, such as cell images and spatial context, by using them to inform prior probabilities of cell type calls. We demonstrate rapid clustering of millions of cells and accurate fine-grained cell typing of kidney and non-small cell lung cancer samples.

bioinformatics↗

Background modeling, Quality Control and Normalization for GeoMx RNA data with GeoDiff

BackgroundNanoStrings GeoMx Digital Spatial Profiler (DSP) RNA assay can measure mRNA from hundreds of regions of customizable shape and size, yet it gives unique challenge in Quality Control(QC) and normalizating due to the omnipresent background noise incurred by the non-specific probe binding, which could not be addressed by conventional methods. Results and discussionUsing Poisson Background model, Background Score Test, Negative Binomial threshold model and Poisson threshold model for normalization from the R package GeoDiff, we perform tasks including size factor estimation, QC and normalization on GoeMx RNA assay data. They are shown to outperform conventional methods like Limit of Quantification for QC as to consistency/false positive rate and 75% quantile normalization as to eliminating technical variability and recovering true signal. ConclusionsWe present a statistical model based workflow for QC and normalizing GeoMx RNA data using GeoDiff, justified by statistical theory and validated by real/simulated data.

bioinformatics↗