Cell Type Knowledge Explorer

* Unique tool for visualization of defining features of individual cell types in primary motor cortex across several modalities simultaneously.
* Provides easy access to underlying BICCN data sets and related data exploration tools such as epigenetics browsers and tools for cell type mapping.
* Comparison of matched cell types across mouse, human, and marmoset via a web portal.
* Ontology engine drives a cell type search and connects these data to external knowledge about cell types.

* The CTKE teaches researchers and students about the defining features of different cell type in primary motor cortex, and how these cell types compare with one another and with matching types across species.
* The CTKE helps researchers to annotate and interpret their own data, by comparing their own data computationally (e.g., mapping single cell RNA-seq data) or visually (e.g., comparison of spatial location or cell morphology) with presented cell types.
* The CTKE provides a jumping point to access many additional data sets and external tools for exploring cell types in primary motor cortex.

* The CTKE helps researchers to annotate and interpret their own data. For example, CTKE includes links to Azimuth, a web application that provides utilities to map single-cell expression data to curated reference datasets. This allows users to derive cell type annotations for their own datasets in the context of BICCN primary motor cortex mini atlas data for the human and mouse. Similarly, CTKE facilitates the interpretation and annotation of other data types. For example, a researcher studying mouse MOp may have immunohistochemistry data indicating that the gene Rorb is highly expressed in a certain population of cells and want more information about what type of cells they might be. Searching “Rorb” in the CTKE would return the L4/5 IT neuron subclass as a cell type that expresses Rorb more highly than other MOp types. Navigating to the “Spatial Transcriptomics” and “Morphology” panels would reveal that L4/5 IT neurons are found at a similar cortical depth and with similar morphological characteristics to those this researcher sees in their cell population of interest. If this researcher were interested in understanding whether these cell types are present in humans, they could navigate to the “Cross-Species Cell Types” panel on the Cell Type Knowledge Card for the L4/5 IT_1 subtype, where they would also find several putatively homologous types and be able to navigate directly to their cards for further investigation.

* The CTKE helps student researchers learn about brain cell types. As single-cell transcriptomics technology advancements have brought new ways to characterize cell types, this knowledge must be conveyed to the next generation in an approachable manner. The CTKE visualization shows the three hierarchical classifications of the cell types (class, subclass, and cell types) and how within cell types it is defined by transcriptomics but contains other modalities (electrophysiological and morphology) in an approachable manner. We have created a 200/300-level undergraduate level lesson explaining the concept of cell types and have students use the CTKE to explore individual cell types further. The lesson has been used at Middlebury College in the Fall of 2023 and planned to be used at Western Washington University in the Spring of 2024. The finalized public version of the lesson will be released by the end of 2024 on our education page (https://alleninstitute.org/education/).

* The CTKE allows researchers to compare their disease models to a standard control. For example, a researcher studying a mouse model of a disease that affects the MOp (i.e., ALS), may do electrophysiological recordings of cells to assess how cells are impacted by disease. After analysis, researchers might notice a difference in the electrophysiological properties (firing patterns, input resistance, firing rate, AP amplitude and/or width, etc.) of their disease model L5 ET cells compared to the healthy control cells listed in the CTKE. To gain a better understanding of which cell types within the L5 ET cell subclass are most affected, researchers can analyze the data provided within CTKE. For example, the L5 ET cell subclass contains four cell types, L5 ET_1, L5 ET_2, L5 ET_3, and L5 ET_4, which express different marker genes. CTKE data show that Npsr1 is a marker gene for L5 ET_4, but not for the other three cell types. Therefore, researchers could perform immunohistochemical staining with an NPSR1 antibody to determine if the cells affected in their disease model specifically belong to the L5 ET_4 cell type. Afterwards, additional immunohistochemical staining could be done for marker genes for the other three L5 ET cell types to determine if their disease model has cell type specific effects or if all L5 ET cells are affected indiscriminately.

* Human
* Marmoset
* Mouse

* This is a first-of-its-kind application that summarizes information about specific cell types across multiple modalities from several publications in a single place.

* This tool does not link to a cell database and therefore is not extensible to other brain regions and cell types in its current form; however, components of this tool with high importance or popularity may be integrated into the Allen Brain Cell (ABC) Atlas (RRID: SCR_024440) later.
* Exploration of the full feature space is possible only through connection to external tools.

* Internet connection

BRAIN Initiative Cell Census Network (BICCN), 2021, A Multimodal Cell Census and Atlas of the Mammalian Primary Motor Cortex, Nature, https://doi.org/10.1038/s41586-021-03950-0

Cell Type Knowledge Explorer tutorial, https://www.youtube.com/watch?v=xJRBQzZLX4s

GitHub repository with scripts and input files for creating web content, https://github.com/AllenInstitute/CTKE_viz

GitHub repository for back-end cell type ontology, https://github.com/obophenotype/brain_data_standards_ontologies

Allen Brain Map Community Forum, https://community.brain-map.org/

Media: August 2023 article on “The Quest to Discover the Cell Types”, https://www.technologynetworks.com/cell-science/articles/the-quest-to-discover-the-cell-types-of-the-brain-378272

Award: DataWorks! “Exemplary Achievement Award for Data Reuse”, https://datascience.nih.gov/director/directors-blog-dataworks-winners-2023

Past workshop: “Navigation and applying cell type taxonomies and tools from the Allen Institute for Brain Science” at IBRO 2023, https://alleninstitute.org/events/ibro2023/

Past workshop: “Satellite Event: Open resources for cell types and taxonomies with the Allen Brain Map” at SfN 2023, https://alleninstitute.org/events/sfn2023/

Future workshop: “Describe Your Neurons Like the Allen Institute” at the Allen Institute April 2024, https://alleninstitute.org/events/describe_your_neurons/

Future webinar series: “Cell Type Taxonomies A-Z”” in 2024 with CTKE the main topics in March and April 2024 (will be recorded for later viewing), https://alleninstitute.org/events/cell_type_az_webinars/