---
title: "Introduction to SRTsim"
author: 
  - name: Jiaqiang Zhu
    affiliation:
    - &umich University of Michigan, Department of Biostatistics
    email: Jiaqiang@umich.edu
date: "`r doc_date()`"
package: "`r pkg_ver('SRTsim')`"
output: 
  BiocStyle::html_document
vignette: >
  %\VignetteIndexEntry{Introduction to SRTsim}
  %\VignetteEngine{knitr::rmarkdown}
  %\VignetteEncoding{UTF-8}
---

```{r, include = FALSE}
knitr::opts_chunk$set(
    collapse = TRUE,
    comment = "#>"
)
```

```{r vignetteSetup, echo=FALSE, message=FALSE, warning = FALSE}
## For links
library("BiocStyle")

## Track time spent on making the vignette
startTime <- Sys.time()

## Bib setup
library("RefManageR")

## Write bibliography information
bib <- c(
    R = citation(),
    BiocStyle = citation("BiocStyle")[1],
    knitr =bibentry(
     bibtype = "InCollection",
     booktitle = "Implementing Reproducible Computational Research",
     title = "knitr: A Comprehensive Tool for Reproducible Research in R",
     author = as.person("Yihui Xie [aut]"),
     editor = as.person("Victoria Stodden, Friedrich Leisch, Roger D. Peng"),
     year = "2014",
     publisher = "Chapman and Hall/CRC",
     isbn = "978-1466561595",
     url = "https://www.routledge.com/Implementing-Reproducible-Research/Stodden-Leisch-Peng/p/book/9781466561595"
   ),
    Matrix = citation("Matrix")[1],
    RefManageR = citation("RefManageR")[1],
    rmarkdown = citation("rmarkdown")[1],
    S4Vectors = citation("S4Vectors")[1],
    sessioninfo = citation("sessioninfo")[1]
)
```
# Welcome

Welcome to the `SRTsim` project! It is composed of:

* a [shiny](https://shiny.rstudio.com/) web application that we are hosting at [https://jiaqiangzhu.shinyapps.io/srtsim](https://jiaqiangzhu.shinyapps.io/srtsim) that can handle a limited set of concurrent users,
* a R package at CRAN that lets you generate the spatially resolved transcriptomic (SRT) data and run a local version of our web application.

The web application allows you to design spatial pattern and generate SRT data with patterns of interest.


# Install `SRTsim`

`R` is an open-source statistical environment which can be easily modified to enhance its functionality via packages. `r CRANpkg('SRTsim')` is a `R` package available via CRAN. `R` can be installed on any operating system from [CRAN](https://cran.r-project.org/) after which you can install `r CRANpkg('SRTsim')` by using the following commands in your `R` session:

```{r 'install', eval = FALSE}
 install.packages("SRTsim")
```

# Run Reference-Based Simulation 

To get started, please load the `r CRANpkg('SRTsim')` package.

```{r setup, message = FALSE, warning = FALSE}
library("SRTsim")
```

Once you have installed the package, we can perform reference-based Tissue-wise simulation with the example data.

```{r 'reference-based tissue-wise simulation'}
## explore example SRT data 
str(exampleLIBD)

example_count   <- exampleLIBD$count
example_loc     <- exampleLIBD$info[,c("imagecol","imagerow","layer")]
colnames(example_loc) <- c("x","y","label")

## create a SRT object
simSRT  <- createSRT(count_in=example_count,loc_in =example_loc)


## Set a seed for reproducible simulation
set.seed(1)

## Estimate model parameters for data generation
simSRT1 <- srtsim_fit(simSRT,sim_schem="tissue")

## Generate synthetic data with estimated parameters
simSRT1 <- srtsim_count(simSRT1)

## Explore the synthetic data
simCounts(simSRT1)[1:5,1:5]
simcolData(simSRT1)
```

We can perform reference-based Domain-specific simulation with the example data.

```{r 'reference-based domain-specific simulation'}

## Set a seed for reproducible simulation
set.seed(1)

## Estimate model parameters for data generation
simSRT2 <- srtsim_fit(simSRT,sim_scheme='domain')

## Generate synthetic data with estimated parameters
simSRT2 <- srtsim_count(simSRT2)

## Explore the synthetic data
simCounts(simSRT2)[1:5,1:5]
```

# Comparison Between Reference Data and Synthetic Data
## Summarized Metrics
After data generation, we can compare metrics of reference data and synthetic data

```{r 'tissue simulation metrics comparison'}

## Compute metrics 
simSRT1   <- compareSRT(simSRT1)

## Visualize Metrics
visualize_metrics(simSRT1)
```

## Expression Patterns For Genes of Interest

```{r 'pattern comparison'}
visualize_gene(simsrt=simSRT1,plotgn = "ENSG00000183036",rev_y=TRUE)
visualize_gene(simsrt=simSRT2,plotgn = "ENSG00000168314",rev_y=TRUE)
```

This work was done by Jiaqiang Zhu, Lulu Shang and Xiang Zhou.

# Reproducibility

The `r CRANpkg('SRTsim')` package was made possible thanks to:

* R `r Citep(bib[['R']])`
* `r Biocpkg('AnnotationHub')` `r Citep(bib[['AnnotationHub']])`
* `r Biocpkg('BiocStyle')` `r Citep(bib[['BiocStyle']])`
* `r Biocpkg('GenomicRanges')` `r Citep(bib[['GenomicRanges']])`
* `r CRANpkg('knitr')` `r Citep(bib[['knitr']])`
* `r CRANpkg('Matrix')` `r Citep(bib[['Matrix']])`
* `r CRANpkg("RefManageR")` `r Citep(bib[["RefManageR"]])`
* `r CRANpkg('rmarkdown')` `r Citep(bib[['rmarkdown']])`
* `r Biocpkg('rtracklayer')` `r Citep(bib[['rtracklayer']])`
* `r Biocpkg('S4Vectors')` `r Citep(bib[['S4Vectors']])`
* `r CRANpkg('sessioninfo')` `r Citep(bib[['sessioninfo']])`


    
Code for creating the vignette

```{r createVignette, eval=FALSE}
## Create the vignette
library("rmarkdown")
system.time(render("SRTsim.Rmd"))

## Extract the R code
library("knitr")
knit("SRTsim.Rmd", tangle = TRUE)
```


Date the vignette was generated.

```{r reproduce1, echo=FALSE}
## Date the vignette was generated
Sys.time()
```

Wallclock time spent generating the vignette.

```{r reproduce2, echo=FALSE}
## Processing time in seconds
totalTime <- diff(c(startTime, Sys.time()))
round(totalTime, digits = 3)
```

`R` session information.

```{r reproduce3, echo=FALSE}
## Session info
library("sessioninfo")
original <- options("width")
options(width = 120)
session_info()
options(original)
```

# Bibliography

This vignette was generated using `r Biocpkg('BiocStyle')` `r Citep(bib[['BiocStyle']])`, `r CRANpkg('knitr')` `r Citep(bib[['knitr']])` and `r CRANpkg('rmarkdown')` `r Citep(bib[['rmarkdown']])` running behind the scenes.

Citations made with `r CRANpkg('RefManageR')` `r Citep(bib[['RefManageR']])`.

```{r vignetteBiblio, results = 'asis', echo = FALSE, warning = FALSE, message = FALSE}
## Print bibliography
PrintBibliography(bib, .opts = list(hyperlink = "to.doc", style = "html"))
```
