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Biology subjects

Schnell, D. J.

Publications and source records attributed to Schnell, D. J..

3 recordsLinked to original sources

Matrix and analysis metadata standards (MAMS) to facilitate harmonization and reproducibility of single-cell data

A large number of genomic and imaging datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While much effort has been devoted to capturing information related to biospecimen information and experimental procedures, the metadata standards that describe data matrices and the analysis workflows that produced them are relatively lacking. Detailed metadata schema related to data analysis are needed to facilitate sharing and interoperability across groups and to promote data provenance for reproducibility. To address this need, we developed the Matrix and Analysis Metadata Standards (MAMS) to serve as a resource for data coordinating centers and tool developers. We first curated several simple and complex "use cases" to characterize the types of featureobservation matrices (FOMs), annotations, and analysis metadata produced in different workflows. Based on these use cases, metadata fields were defined to describe the data contained within each matrix including those related to processing, modality, and subsets. Suggested terms were created for the majority of fields to aid in harmonization of metadata terms across groups. Additional provenance metadata fields were also defined to describe the software and workflows that produced each FOM. Finally, we developed a simple listlike schema that can be used to store MAMS information and implemented in multiple formats. Overall, MAMS can be used as a guide to harmonize analysis-related metadata which will ultimately facilitate integration of datasets across tools and consortia. MAMS specifications, use cases, and examples can be found at https://github.com/single-cell-mams/mams/.

bioinformatics↗

A Chloroplast Protein Atlas Reveals Novel Structures and Spatial Organization of Biosynthetic Pathways

Chloroplasts are eukaryotic photosynthetic organelles that drive the global carbon cycle. Despite their importance, our understanding of their protein composition, function, and spatial organization remains limited. Here, we determined the localizations of 1,032 candidate chloroplast proteins by using fluorescent protein tagging in the model alga Chlamydomonas reinhardtii. The localizations provide insights into the functions of hundreds of poorly-characterized proteins, including identifying novel components of nucleoids, plastoglobules, and the pyrenoid. We discovered and further characterized novel organizational features, including eleven chloroplast punctate structures, cytosolic crescent structures, and diverse unexpected spatial distributions of enzymes within the chloroplast. We observed widespread protein targeting to multiple organelles, identifying proteins that likely function in multiple compartments. We also used machine learning to predict the localizations of all Chlamydomonas proteins. The strains and localization atlas developed here will serve as a resource to enable studies of chloroplast architecture and functions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/493820v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@19c871eorg.highwire.dtl.DTLVardef@16ac46corg.highwire.dtl.DTLVardef@859b7dorg.highwire.dtl.DTLVardef@1a3446e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LI1,032 candidate chloroplast proteins localized by fluorescent tagging. C_LIO_LIThis protein atlas reveals novel chloroplast structures, functional regions, and components. C_LIO_LIPrevalent dual-organelle localization suggests extensive cross-compartment coordination. C_LIO_LIAtlas-trained machine learning predicts localizations of all C. reinhardtii proteins. C_LI

plant biology↗

DoubletDecon: Cell-State Aware Removal of Single-Cell RNA-Seq Doublets

Methods for single-cell RNA sequencing (scRNA-Seq) have greatly advanced in recent years. While droplet- and well-based methods have increased the capture frequency of cells for scRNA-Seq, these technologies readily produce technical artifacts, such as doublet-cell and multiplet-cell captures. Doublets occurring between distinct cell-types can appear as hybrid scRNA-Seq profiles, but do not have distinct transcriptomes from individual cell states. We introduce DoubletDecon, an approach that detects doublets with a combination of deconvolution analyses and the identification of unique cell-state gene expression. We demonstrate the ability of DoubletDecon to identify synthetic and cell-hashing cell singlets and doublets from scRNA-Seq datasets of varying cellular complexity. DoubletDecon is able to account for cell-cycle effects and is compatible with diverse species and unsupervised population detection algorithms (e.g., ICGS, Seurat). We believe this approach has the potential to become a standard quality control step for the accurate delineation of cell states.

bioinformatics↗