Figure - available from: Nature Communications
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GeneVector Framework Overview of GeneVector framework starting from single cell read counts. Mutual information is computed on the joint probability distribution of read counts for each gene pair. Each pair is used to train a single layer neural network where the MSE loss is evaluated from the model output (w1Tw2) with the mutual information between genes. From the resulting weight matrix, a gene embedding, cell embedding, and co-expression similarity graph are constructed. Using vector space arithmetic, downstream analyses include identification of cell-specific metagenes, batch effect correction, and cell type classification.
Source publication
Deciphering individual cell phenotypes from cell-specific transcriptional processes requires high dimensional single cell RNA sequencing. However, current dimensionality reduction methods aggregate sparse gene information across cells, without directly measuring the relationships that exist between genes. By performing dimensionality reduction with...
Citations
Although allogeneic hematopoietic cell transplantation (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of post-transplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures at diagnosis and post-transplant relapse in bone marrow samples from four pediatric patients using a multimodal single-cell proteogenomic approach. Downregulation of MHC class II expression was most profound in progenitor-like blasts and accompanied by correlative changes in transcriptional regulation. Dysfunction of activated NK cells and CD8+ T-cell subsets at relapse was evidenced by loss of response to IFN-γ, TNF-α signaling via NF-kβ, and IL-2/STAT5 signaling. Clonotype analysis of post-transplant relapse samples revealed expansion of dysfunctional T cells and enrichment of T-regulatory and T-helper cells. Using novel computational methods, our results illustrate a diverse immune-related transcriptional signature in post-transplant relapses not previously reported in pediatric AML.
