The recent development of multimodal single-cell technology has made the possibility of acquiring multiple omics data from individual cells, thereby enabling a deeper understanding of cellular states and dynamics. Nevertheless, the proliferation of multimodal single-cell data also introduces tremendous challenges in modeling the complex interactions among different modalities. The recently advanced methods focus on constructing static interaction graphs and applying graph neural networks (GNNs) to learn from multimodal data. However, such static graphs can be suboptimal as they do not take advantage of the downstream task information; meanwhile GNNs also have some inherent limitations when deeply stacking GNN layers. To tackle these issues, in this work, we investigate how to leverage transformers for multimodal single-cell data in an end-to-end manner while exploiting downstream task information. In particular, we propose a framework which can readily incorporate external domain knowledge and model the interactions within each modality and cross modalities. Extensive experiments demonstrate that achieves superior performance on various benchmark datasets. Remarkably, won a Kaggle silver medal with the rank of 24/1221 (Top 2%) in a NeurIPS 2022 competition. Our implementation is publicly available at Github.
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PLoS Genet
January 2025
Department of Biology, Boston University, Boston Massachusetts, United States of America.
The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Allen Institute for Brain Science, Seattle, WA, USA.
Background: Numerous studies have identified AD-associated molecular and cellular changes to the cortex using single nucleus RNA sequencing (snRNA-seq) and, to a lesser extent, single nucleus ATAC-seq (snATAC-seq), applied to millions of cells across hundreds of donors. It has proven challenging, however, to determine whether changes are consistent because of differences in cohort selection, reported clinical metadata, data pre-processing, cellular taxonomy construction/mapping, and analytical strategies across studies.
Method: We uniformly re-processed 10 publicly available datasets (Table 1) that had applied snRNA-seq to 4.
Braz J Phys Ther
December 2024
Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, 3000, Leuven, Belgium; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven 3000, Leuven, Belgium; KU Leuven Cancer Institute (LKI), KU Leuven 3000, Leuven, Belgium.
Res Sq
December 2024
Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA.
Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX.
View Article and Find Full Text PDFRes Sq
December 2024
The Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Single-cell RNA sequencing (scRNA-seq) has revolutionized cell biology by enabling the profiling of transcriptomes at a single-cell resolution, leading to important discoveries that have advanced our understanding of cellular and tissue heterogeneity, developmental trajectories, and disease progression. Despite these important advances, scRNA-seq is limited to measuring the transcriptome providing a partial view of cellular function. To address this limitation, multimodal scRNA-seq assays have emerged, allowing for the simultaneous measurement of RNA expression and protein.
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