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Vanderaa, C.

Publications and source records attributed to Vanderaa, C..

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Curated Single Cell Multimodal Landmark Datasets for R/Bioconductor

BackgroundThe majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal profiling methods add simultaneous measurement of genomic, proteomic, epigenetic, and/or spatial information on the same cells. The development of new statistical and computational methods in Bioconductor for such data will be facilitated by easy availability of landmark datasets using standard data classes. ResultsWe collected, processed, and packaged publicly available landmark datasets from important single-cell multimodal protocols, including CITE-Seq, ECCITE-Seq, SCoPE2, scNMT, 10X Multiome, seqFISH, and G&T. We integrate data modalities via the MultiAssayExperiment Bioconductor class, document and re-distribute datasets as the SingleCellMultiModal package in Bioconductors Cloud-based ExperimentHub. The result is single-command actualization of landmark datasets from seven single-cell multimodal data generation technologies, without need for further data processing or wrangling in order to analyze and develop methods within Bioconductors ecosystem of hundreds of packages for single-cell and multimodal data. ConclusionsWe provide two examples of integrative analyses that are greatly simplified by SingleCellMultiModal. The package will facilitate development of bioinformatic and statistical methods in Bioconductor to meet the challenges of integrating molecular layers and analyzing phenotypic outputs including cell differentiation, activity, and disease. Author SummaryExperimental data packages that provide landmark datasets have historically played an important role in the development of new statistical methods in Bioconductor by lowering the barrier of access to relevant data, providing a common testing ground for software development and benchmarking, and encouraging interoperability around common data structures. In this manuscript, we review major classes of technologies for collecting multimodal data including genomics, transcriptomics, epigenetics, proteomics, and spatial information at the level of single cells. We present the SingleCellMultiModal R/Bioconductor package that provides single-command access to landmark datasets from seven different technologies, storing datasets using HDF5 and sparse arrays for memory efficiency and integrating data modalities via the MultiAssayExperiment class. We demonstrate two integrative analyses that are greatly simplified by SingleCellMultiModal. The package facilitates development and benchmarking of bioinformatic and statistical methods to integrate molecular layers at the level of single cells with phenotypic outputs including cell differentiation, activity, and disease, within Bioconductors ecosystem of hundreds of packages for single-cell and multimodal data.

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Utilizing scp for the analysis and replication of single-cell proteomics data

IntroductionMass spectrometry-based proteomics is actively embracing quantitative, single-cell level analyses. Indeed, recent advances in sample preparation and mass spectrometry (MS) have enabled the emergence of quantitative MS-based single-cell proteomics (SCP). While exciting and promising, SCP still has many rough edges. The current analysis workflows are custom and built from scratch. The field is therefore craving for standardized software that promotes principled and reproducible SCP data analyses. Areas coveredThis special report is the first step toward the formalization and standardization of SCP data analysis. scp, the software that accompanies this work, successfully replicates one of the landmark SCP studies and is applicable to other experiments and designs. We created a repository containing the replicated workflow with comprehensive documentation in order to favor further dissemination and improvements of SCP data analyses. Expert opinionReplicating SCP data analyses uncovers important challenges in SCP data analysis. We describe two such challenges in detail: batch correction and data missingness. We provide the current state-of-the-art and illustrate the associated limitations. We also highlight the intimate dependence that exists between batch effects and data missingness and offer avenues for dealing with these exciting challenges. 1 Article highlightsO_LISingle-cell proteomics (SCP) is emerging thanks to several recent technological advances, but further progress is still lagging due to the lack of principled and systematic data analysis. C_LIO_LIThis work offers a standardized solution for the processing of SCP data demonstrated by the replication of a landmark SCP work. C_LIO_LITwo important challenges remain: batch effects and data missingness. Furthermore, these challenges are not independent and therefore need to be modeled simultaneously. C_LI

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