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Last updated: 2024-06-15

Checks: 1 1

Knit directory: duplex_sequencing_screen/

This reproducible R Markdown analysis was created with workflowr (version 1.6.2). The Checks tab describes the reproducibility checks that were applied when the results were created. The Past versions tab lists the development history.

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R Markdown file: uncommitted changes

The R Markdown file has unstaged changes. To know which version of the R Markdown file created these results, you’ll want to first commit it to the Git repo. If you’re still working on the analysis, you can ignore this warning. When you’re finished, you can run wflow_publish to commit the R Markdown file and build the HTML.

Repository version: e57e36e

Great! You are using Git for version control. Tracking code development and connecting the code version to the results is critical for reproducibility.

The results in this page were generated with repository version e57e36e. See the Past versions tab to see a history of the changes made to the R Markdown and HTML files.

Note that you need to be careful to ensure that all relevant files for the analysis have been committed to Git prior to generating the results (you can use wflow_publish or wflow_git_commit). workflowr only checks the R Markdown file, but you know if there are other scripts or data files that it depends on. Below is the status of the Git repository when the results were generated:

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Note that any generated files, e.g. HTML, png, CSS, etc., are not included in this status report because it is ok for generated content to have uncommitted changes.

---

These are the previous versions of the repository in which changes were made to the R Markdown (analysis/index.Rmd) and HTML (docs/index.html) files. If you’ve configured a remote Git repository (see ?wflow_git_remote), click on the hyperlinks in the table below to view the files as they were in that past version.

File	Version	Author	Date	Message
Rmd	e57e36e	haiderinam	2024-04-29	Added ABL full kinase analyses
html	e57e36e	haiderinam	2024-04-29	Added ABL full kinase analyses
Rmd	268b0cf	haiderinam	2023-09-02	Added lane25a data (Shokat lab screens)
html	268b0cf	haiderinam	2023-09-02	Added lane25a data (Shokat lab screens)
Rmd	57fd1e7	haiderinam	2023-08-30	Updated various analyses and added to website
html	57fd1e7	haiderinam	2023-08-30	Updated various analyses and added to website
html	f9eea37	haiderinam	2023-08-30	2023 Updates
Rmd	8202ef7	haiderinam	2023-04-10	Added BE vs SM analyses on putative mutant
html	8202ef7	haiderinam	2023-04-10	Added BE vs SM analyses on putative mutant
Rmd	60b906b	haiderinam	2023-04-10	Added ROC analyses on BE-SM data
html	60b906b	haiderinam	2023-04-10	Added ROC analyses on BE-SM data
Rmd	a33eea5	haiderinam	2023-03-25	Added ABL CDF Analyses of evenness
html	a33eea5	haiderinam	2023-03-25	Added ABL CDF Analyses of evenness
Rmd	81a5af3	haiderinam	2023-02-25	Added shortest codon finder function
Rmd	fa7baf1	haiderinam	2022-12-15	Updates to the variant caller
html	fabfb30	haiderinam	2022-12-09	Build site.
Rmd	077edd0	haiderinam	2022-12-09	Added K562 Webpage
html	077edd0	haiderinam	2022-12-09	Added K562 Webpage
Rmd	cec2e31	haiderinam	2022-12-08	Added error rate analyses
html	cec2e31	haiderinam	2022-12-08	Added error rate analyses
html	404fc72	haiderinam	2022-11-04	Build site.
Rmd	ff4b4e8	haiderinam	2022-11-04	wflow_publish("analysis/index.Rmd")
Rmd	3a2f887	haiderinam	2022-11-04	Added analyses of IL3 independence
Rmd	6f54acf	haiderinam	2022-11-04	Added analyses of SSCS vs DCS error rates
html	28519e7	haiderinam	2022-10-29	Build site.
Rmd	ba25cb7	haiderinam	2022-10-29	wflow_publish("analysis/index.Rmd")
Rmd	7ed0af8	haiderinam	2022-08-22	August 2022 Updates
html	86ce8ca	haiderinam	2022-08-22	August 2022 Update
html	f368371	haiderinam	2020-08-13	Build site.
html	7fe0f9b	haiderinam	2020-07-06	Build site.
Rmd	e4a901d	haiderinam	2020-07-06	wflow_publish("analysis/index.Rmd")
html	231d21d	haiderinam	2020-06-07	Build site.
html	8f50f99	haiderinam	2020-06-07	Build site.
Rmd	5da3af0	haiderinam	2020-06-07	wflow_publish("analysis/index.Rmd")
html	75ddcb1	haiderinam	2020-06-02	Build site.
Rmd	a173683	haiderinam	2020-06-02	wflow_publish("analysis/index.Rmd")
html	bd2dec5	haiderinam	2020-06-02	Build site.
Rmd	1bb5940	haiderinam	2020-06-02	wflow_publish("analysis/index.Rmd")
html	c43acef	haiderinam	2020-06-02	Build site.
Rmd	d5c9f64	haiderinam	2020-06-02	wflow_publish("analysis/index.Rmd")
html	eaca616	haiderinam	2020-04-20	Build site.
Rmd	2bba93e	haiderinam	2020-04-20	wflow_publish("analysis/*.Rmd")
html	05e3df6	haiderinam	2020-04-07	Build site.
html	1c86f69	haiderinam	2020-04-07	Build site.
Rmd	e731909	haiderinam	2020-04-07	wflow_publish("analysis/index.Rmd")
html	4516a7f	haiderinam	2020-04-06	Build site.
Rmd	3a57291	haiderinam	2020-04-06	wflow_publish(files = "analysis/index.Rmd")
html	c2930d5	haiderinam	2020-04-03	Build site.
Rmd	52f6884	haiderinam	2020-04-03	wflow_publish("analysis/*.Rmd")
html	6af2cdc	haiderinam	2020-04-03	Build site.
Rmd	5cda9d3	haiderinam	2020-04-03	wflow_publish("analysis/*.Rmd")
html	0b9b87b	haiderinam	2020-04-02	Build site.
Rmd	fc5b9c0	haiderinam	2020-04-02	wflow_publish("analysis/*.Rmd")
html	2bce927	haiderinam	2020-04-02	Build site.
html	4ed9b35	haiderinam	2020-04-02	Build site.
Rmd	e31836a	haiderinam	2020-04-02	wflow_publish("analysis/*.Rmd")
html	99181d5	haiderinam	2020-04-02	Build site.
Rmd	17c01d4	haiderinam	2020-04-02	wflow_publish("analysis/index.Rmd")
html	1e2f469	haiderinam	2020-04-02	Build site.
html	e11eec5	haiderinam	2020-04-02	Build site.
Rmd	0053f96	haiderinam	2020-04-02	wflow_publish("analysis/*.Rmd")
html	b1cbbfa	haiderinam	2020-04-02	Build site.
Rmd	703346a	haiderinam	2020-04-02	Start workflowr project.

---

Duplex Sequencing Spike-Ins

• Click here for the script that reads BCRABL dose response data, and fits it to a 4-parameter dose response curve.
  

• Click here for the script that reads mutation annotation data and generates dataframes with annotated variants and the correct cell counts

• Click here for initial growth rate plots
  

• Click here for growth rate plots for ENU mutants
  

• Click here for analysis looking at whether we achieved our desired depth of coverages

• Click here for analysis looking at how well our data predicts BCRABL clinical abundance compared to conventional IC50s

• Click here for method to obtain confidence intervals on growth rates from IC50 measurements. Plotted alongside observed growth rate data, these confidence intervals show how well our pooled data matches predictions based off of IC50s. (Needs updates in methodology)
  

• Click here for analyses of replicate to replicate agreement between the spike in replicates. Also includes this analysis for the mutagenesis replicates. Also includes the agreement in observed vs predicted depth of coverages for all sequencing pools. Note: this analysis does not include dosage corrections that improves replicate to replicate heterogeneity.
  

• Click here to see analysis of predictions based on Enrich2 vs Shendure vs our method

• Click here for our dosing normalization strategy
  

• Click here for simulations showing enrichment and depletion events in a 3 mutant pool.

• Click here showing the conformity between the growth rates in the presence of drug measured at a low MAF via FACs, sequencing, and via IC50 studies for a single mutant.
  

• Click here to view BCRABL Imatinib heatmaps generated using CRISPR-cut libraries

• Click here to view preliminary BCRABL Imatinib and Asciminib heatmaps made with enzymatically sheared libraries

• Click here and to view iL3 independence data and here to view iL3 independence heatmap and here to view imatinib heatmaps on enzymatically sheared data

• Click here to view error rates without barcodes, with single strand consensi, and with duplex consensus sequencing.

• Click here to view the results of the BCRABL Library transduced in K562 Cells

• Click here to view analyses of the CDFs of our saturating mutagenesis libraries. These show how even or uneven the libraries are at different stages of the screening process.
  

• Click here to view analyses in which we compared base editing and saturating mutagenesis data on ABL. This is followed by analysis in which we decide on filter cutoffs for enrichment scores to detect signficantly depleting mutants that drop out for IL3 independence in BaF3s.
  

• Click here to view analyses in which we predicted admixtures of mutants made by sgRNAs in Base Editing Screens. We then used the saturating mutagenesis data to predict the fitness of these sgRNAs.
  

• Click here to view initial kinase function analyses.
  

• Click here to view our analyses of whether mutants in the cosmic/sanger database are resistant according to our screens.
  .

• Click here to view our analyses of imatinib resistance in the full ABL kinase. This includes heatmaps, scatterplots, boxplots, waterfall plots, all analyzing the imatinib resistance profile of the ABL kinase.
  .

• Click here to view our analyses of how SNPs in Gnomad enable potentially drug resistant mutants, necessitating the study of multi-nucleotide variants in DMS screens.
  .

Click here to be redirected to the github page that contains all the data and analysis rmd files.

What is in each directory:

• Data: contains data downloaded prior to analyses.
  
• Output: contains data that the code makes
  
• Analysis: contains your Rmarkdown files with the code.
  
• Docs: contain the html output from the Rmd files in the analysis directory.
  
• Code: contains .R files that are functions that the Rmd files in the analysis folder use.