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Lee0498 committed Mar 25, 2024
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Expand Up @@ -16,23 +16,38 @@ address it with scRank using a target-perturbed gene regulatory network (tpGRN)
#devtools::install_github("rikenbit/rTensor")
devtools::install_github("ZJUFanLab/scRank")
```

## Note

### Key Updates
- **Disease Relevance and Drug Effects Analysis:** Introducing the new `scRank_GSEA()` and `plot_drug_function()` functions for analyzing disease relevance and drug effects in the highest-ranking cell types.
- **Drug Type Specification:** Added a `type` parameter in `rank_celltype()` to specify modeling effects of either agonists or antagonists, enhancing the versatility of drug response modeling.
- **Efficient Large Matrix Manipulations:** Integration of the Python module "tensorly" in the `Constr_net()` function, with a new parameter `use_py`, to optimize large-scale data processing.
- **Enhanced Cell State Discernment:** Integration of the `scSHC` algorithm into the `CreateScRank()` function with an `if_cluster` parameter, improving the tool's ability to discern various cell states. [More about scSHC](https://github.com/igrabski/sc-SHC).
- **Incorporating Drug Resistance Mechanisms:** The `resistance_target` parameter in `rank_celltype()` allows for inputting targets of alternative pathways, aiding in the consideration of drug resistance mechanisms.
- **Flexible Edge Weight Adjustment:** Introduction of the `keep_ratio` parameter to adjust edge weights in the gene regulatory network, allowing for differential treatment of node types.

### To-Do
- **Packaging and Accessibility:** We are in the process of submitting scRank to Bioconductor or CRAN for enhanced accessibility.
## Overview
scRank method consists of two components, wherein the first is to reconstruct the gene regulatory network from expression ptrofiles using `Constr_net` function and the second step is to estimate the effect of the in silico drug perturbation for GRNs in each cell type using `rank_celltype` function.
scRank method consists of two components, wherein the first is to reconstruct the gene regulatory network from expression ptrofiles using `Constr_net` function and the second step is to estimate the extent of the in silico drug perturbation for GRNs in each cell type using `rank_celltype` function.

scRank start with create a S4 object by `CreateScRank` function:
- the `input` is the gene expression profil eand `meta` is the cell type information.
- `cell_type` is the column name of the cell type information in `meta`
- `species` is the species of the data. ("mouse" or "human")
- `drug` is the drug name and `target` is the target gene of the drug. `drug` could be any inhibitor in our database `utile_database`. if you know the specific target gene of the drug, you can input the target gene into `target` without inputing `drug`.
- `drug` is the drug name and `target` is the target gene of the drug. `drug` could be found in our database `utile_database`. if you know the specific target gene of the drug, you can input the target gene into `target` without inputing `drug`.
- `type` characters meaning the MOAs of drug including antagonist or agonist. Default is antagonist.
- `if_cluster` A logical meaning whether clustering single-cell transcriptomic data. Default is `FALSE`.

```{r}
CreateScRank <- function(input,
meta,
cell_type,
species,
drug,
target)
target,
type,
if_cluster)
```

The format of the `input` is as follows:
Expand All @@ -54,6 +69,7 @@ we load the demo dataset from Seurat object, the drug target is known as Brd4.

```{r}
seuratObj <- system.file("extdata", "AML_object,rda", package="scRank")
load(seuratObj)
obj <- CreateScRank(input = seuratObj,
species = 'mouse',
cell_type = 'label',
Expand All @@ -73,9 +89,10 @@ obj <- scRank::rank_celltype(obj)
the final infered rank of cell types that determine the drug response is stored in `obj@cell_type_rank`

### 4. Visualize the result
For visulizing the rank of cell types in dimension reduction space, we can use the `plot_dim` function.
For visulizing the rank of cell types in dimension reduction space, we can use the `plot_dim` function after `init_mod()`.

```{r}
obj <- init_obj(obj)
plot_dim(obj)
```
<img src='https://github.com/ZJUFanLab/scRank/blob/main/img/scRank_data.png'>
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