#30 · Single-cell
Constrained optimization for marker selection, deconvolution and cell identity
The dominant thread is explicit formulation of inference as an optimization problem over single-cell, spatial and bulk accessibility data. WAD deconvolves cell-type proportions from bulk ATAC-seq via wavelet-based L1-minimal linear programming, while SepSolve selects small marker sets through a linear program that enforces c-separation of cell types. geneCover offers a label-free route to minimally redundant marker panels from gene-gene correlations, and SIID uses joint nonnegative factorization to impute and deconvolve genes across paired Xenium and Visium platforms. ALPINE applies supervised nonnegative matrix factorization to separate technical from phenotypic factors in multicondition data. The subspace clustering method models each cell type as an affine subspace of linear constraints on scRNA-seq profiles. What is new is the constraint or objective itself, such as L1 reconstruction loss, c-separation or affine subspace membership, used as the basis of identity and composition inference.
Published papers
Removal of unwanted variation in pseudobulk analysis of single-cell RNA sequencing data and the leveraging of pseudoreplicates.
Benchmarks RUV2, RUVIII, RUV4 implementation strategies for pseudobulked scRNA-seq and introduces RUVIII PBPS to control FDR without technical replicates or…
Preprints
Copula modeling of gene coexpression in single-cell RNA sequencing data
Benchmarks six copula models for gene coexpression in scRNA-seq data; Gaussian copulas balance accuracy and speed, while vine copulas scale poorly.
COBRA: Cell-type-specific Orthogonal Batch effect Removal Algorithm in single cell RNA-sequencing data
COBRA is a linear-model batch correction method for scRNA-seq that adjusts cell-type-specific batch effects in the full gene space, with iterative…
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