The Human BioMolecular Atlas Program (HuBMAP) aims to create a multi-scale spatial atlas of the healthy human body at single-cell resolution by applying advanced technologies and disseminating resources to the community. As the HuBMAP moves past its first phase, creating ontologies, protocols and pipelines, this Perspective introduces the production phase: the generation of reference spatial maps of functional tissue units across many organs from diverse populations and the creation of mapping tools and infrastructure to advance biomedical research.HuBMAP was founded with the goal of establishing state-of-the-art frameworks for building spatial multiomic maps of non-diseased human organs at single-cell resolution 1 . During the first phase (2018)(2019)(2020)(2021)(2022), the priorities of the project included the validation and development of assay platforms; workflows for data processing, management, exploration and visualization; and the establishment of protocols, quality control standards and standard operating procedures. Extensive infrastructure was established through a coordinated effort among the various HuB-MAP integration, visualization and engagement teams, tissue-mapping centres, technology and tools development and rapid technology implementation teams and working groups 1 . Single-cell maps, predominantly consisting of two-dimensional (2D) spatial data as well as data from dissociated cells, were generated for several organs. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) was established for open access to experimental tissue data and reference atlas data.The infrastructure was augmented with software tools for tissue data registration, processing, annotation, visualization, cell segmentation and automated annotation of cell types and cellular neighbourhoods from spatial data. Computational methods were developed for integrating multiple data types across scales and interpretation 2 . Standard reference terminology and a common coordinate framework spanning anatomical to biomolecular scales were established to ensure interoperability across organs, research groups and consortia 3 . Guidelines to capture high-quality multiplexed spatial data 4 were established including validated panels of cell-and structure-specific antibodies 5 . The first phase produced a large number of manuscripts (https://commonfund.nih.gov/ publications?pid=43) including spatially resolved single-cell maps [6][7][8][9][10][11] .The production phase of HuBMAP was launched in the autumn of 2022. The focus is on scaling data production spanning diverse biological variables (for example, age and ethnicity) and deployment and enhancement of analytical, visualization and navigational tools to generate high-resolution 3D accessible maps of major functional tissue units from more than 20 organs. This phase involves over 60 institutions and 400 researchers with opportunities for active intra-and inter-consortia collaborations and building a foundational resource for new biological insights and precision medicine. Below, ...
The lack of understanding as to the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies and biomarkers. Here, to address this gap, we analysed 740,000 single nuclei RNAseq profiles of 165 samples of white matter (WM) lesions, normal appearing WM, grey matter (GM) lesions and normal appearing GM from 55 MS patients and 28 controls. We find that gene expression changes in response to MS are highly cell-type specific in WM and GM lesions but are largely shared within an individual cell-type across lesions, following a continuum rather than discrete lesion-specific molecular programs. The major biological determinants of variability in gene expression in MS samples relate to individual patient effects, rather than to lesion types or other metadata. Using multi-omics factor analysis (MOFA+), we identify three subgroups of MS patients with distinct oligodendrocyte composition and WM glial gene expression signatures, suggestive of engagement of different pathological/regenerative processes. The discovery of these three patterns significantly advances our mechanistic understanding of progressive MS, provides a framework to use molecular biomarkers to stratify patients for best therapeutic approaches for progressive MS, and highlights the need for precision-medicine approaches to address heterogeneity among MS patients.
Spatially resolved omics technologies are transforming our understanding of biological tissues. However, handling uni- and multi-modal spatial omics datasets remains a challenge owing to large volumes of data, heterogeneous data types and the lack of unified spatially-aware data structures. Here, we introduce SpatialData, a framework that establishes a unified and extensible multi-platform file-format, lazy representation of larger-than-memory data, transformations, and alignment to common coordinate systems. SpatialData facilitates spatial annotations and cross-modal aggregation and analysis, the utility of which is illustrated via multiple vignettes, including integrative analysis on a multi-modal Xenium and Visium breast cancer study.
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