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bio-la authored Mar 6, 2024
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normalization_methods
different_entry_points
setup_for_spatial_workflows
integration_methods
```
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# Integration methods implemented in panpipes

The panpipes integration pipeline implements a variety of tools to batch correct individual modalities and/or integrate across modalities to produce a reduced dimension representation of the dataset.<br>
There are different tools available for each modality such as RNA (also referred to as GEX), PROT (can be referred to as ADT) and ATAC which can be run as required before running `panpipes integration make merge_batch_correction`
to create the final object with the reduced dimension represented.<br>

The ideal way to run `panpipes integration` is to use the output `MuData`file from `panpipes preprocess` since it will already be in the required format.
However, if using independent MuData the object should contain normalised data in the X slot of each modality, a ‘raw_counts’ layer in each modality, and a sample_id column in each slot of the obs and the outer obs.

The following table describes the different methods of batch correction available and their specificities:

| Method | type of integration | modalities | code | references | benchmarks paper |
|-----------|-----------------------------|-----------------|-----------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------|
| harmony | unimodal (batch correction) | rna, atac, prot | [harmony](https://github.com/immunogenomics/harmony) | [Korsunsky  et al 2019](https://www.nature.com/articles/s41592-019-0619-0) | [Luecken et al 2022](https://www.nature.com/articles/s41592-021-01336-8) |
| BBKNN | unimodal (batch correction) | rna, atac, prot | [BBKNN](https://github.com/Teichlab/bbknn) | [Polański et al 2020](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883685/) | [Luecken et al 2022](https://www.nature.com/articles/s41592-021-01336-8) |
| Scanorama | unimodal (batch correction) | rna | [Scanorama](https://github.com/brianhie/scanorama) | [Hie, Bryson, and  Berger 2019](https://pubmed.ncbi.nlm.nih.gov/31061482/) | [Luecken et al 2022](https://www.nature.com/articles/s41592-021-01336-8) |
| scVI | unimodal (batch correction) | rna | [scVI](https://github.com/scverse/scvi-tools) | [Gayoso et al 2022](https://www.nature.com/articles/s41587-021-01206-w) | [Luecken et al 2022](https://www.nature.com/articles/s41592-021-01336-8) |
| MultiVI | multimodal | atac, rna | [MultiVI](https://github.com/scverse/scvi-tools) | [Ashuach et al 2023](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406609/) | [Lee, Kaestner, and Li 2023](https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03073-x) |
| totalVI | multimodal | prot, rna | [totalVI](https://github.com/scverse/scvi-tools) | [Gayoso  et al. 2021](https://pubmed.ncbi.nlm.nih.gov/33589839/) | [Makrodimitris et al 2024](https://academic.oup.com/bib/article/25/1/bbad416/7450271) |
| MOFA | multimodal | rna, atac, prot | [MOFA](https://github.com/bioFAM/mofapy2) | [Argelaguet et al 2020](https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-02015-1) | [Lee, Kaestner, and Li 2023](https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03073-x) |
| WNN | multimodal | rna, atac, prot | [WNN](https://muon.readthedocs.io/en/latest/api/generated/muon.pp.neighbors.html) | [Hao et al 2021](https://pubmed.ncbi.nlm.nih.gov/34062119/) | [Lee, Kaestner, and Li 2023](https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03073-x) |
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The ideal way to run `panpipes integration` is to use the output `MuData` file from `panpipes preprocess`, as this will make sure the MuData object has correctly names layers and slots.

The MuData object required should contain normalised data in the X slot of each modality, a 'raw_counts' layer in each modality, and a sample_id column in each slot of the obs and the outer obs. A plus is a PCA in the obsm slot for each modality, if not it will be calculated on the flight with default parameters.

## Algorithms supported by panpipes for uni and multimodal integration
Please check [Integration methods implemented in panpipes](https://github.com/DendrouLab/panpipes/blob/docs_g/docs/usage/integration_methods.md) for a description of the algorithms and source references for the methods used in the integration step.

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