Existing solutions

*Integrating single-cell transcriptomic data across different conditions, technologies, and species, Butler A, et al. Nature Biotechnology, 2018

Existing solutions

Align samples

scVI, Conos, ..., Seurat

See the review from the Theis lab

*Integrating single-cell transcriptomic data across different conditions, technologies, and species, Butler A, et al. Nature Biotechnology, 2018

Existing solutions

Align samples

Perform joint annotation

*Integrating single-cell transcriptomic data across different conditions, technologies, and species, Butler A, et al. Nature Biotechnology, 2018

Existing solutions

Align samples

Perform joint annotation

Run differential expression 

*Single-cell genomics identifies cell type–specific molecular changes in autism, Velmeshev D, et al. Science, 2019

Existing solutions

Align samples

Perform joint annotation

Run differential expression 

Run Gene Ontology analysis

*Single-cell genomics identifies cell type–specific molecular changes in autism, Velmeshev D, et al. Science, 2019

Existing solutions

Align samples

Perform joint annotation

Run differential expression 

Run Gene Ontology analysis

Compare cell type proportions

*A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation, Grubman A, Nature Neuroscience, 2019

Existing solutions

Align samples

Perform joint annotation

Run differential expression 

Run Gene Ontology analysis

• A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation, Grubman A, Nature Neuroscience (2019).

• Single-cell genomics identifies cell type–specific molecular changes in autism, Velmeshev D, et al. Science (2019).

• Mathys, H., Davila-Velderrain, J., Peng, Z. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019).

• Schirmer, L., Velmeshev, D., Holmqvist, S. et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82 (2019).

• Wheeler, M.A., Clark, I.C., Tjon, E.C. et al. MAFG-driven astrocytes promote CNS inflammation. Nature 578, 593–599 (2020).

Compare cell type proportions

Composition analysis, cluster-based

Composition analysis, cluster-based

Problem: changes are not independent

Composition analysis, cluster-based

*Schirmer, L., Velmeshev, D., Holmqvist, S. et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82 (2019)

Old

Composition analysis, cluster-free

*Schirmer, L., Velmeshev, D., Holmqvist, S. et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82 (2019)

Composition analysis, cluster-free

*Schirmer, L., Velmeshev, D., Holmqvist, S. et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82 (2019)

Improved z-scores

Expression analysis, cluster-based

What cell types are affected the most?

Expression analysis, cluster-based

Visualization of sample structure

*Single-cell genomics identifies cell type–specific molecular changes in autism, Velmeshev D, et al. Science (2019)

Expression analysis, cluster-based

Visualization of sample structure

*Single-cell genomics identifies cell type–specific molecular changes in autism, Velmeshev D, et al. Science (2019)

Expression analysis, cluster-based

Visualization of sample structure

*A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation, Grubman A, Nature Neuroscience, 2019