Overview of this repo

This repo houses all of the code and analysis conducted for the manuscript "Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis". A link to the raw fastq file data hosted on GEO is provided here. The abstract for the manuscript is copied below:

Abstract

Patients infected with Leishmania braziliensis develop chronic lesions that often fail to respond to treatment. To determine whether genes whose expression is highly variable in lesions might influence disease outcome, we obtained biopsies of lesions from patients prior to drug treatment, performed transcriptomic profiling, and identified highly variable genes whose expression correlated with treatment outcome. Amongst the most variable genes were components of the cytolytic pathway, the expression of which appeared to be driven by parasite load in the skin. We demonstrated that treatment failure can be directly linked to the cytolytic pathway activated during infection. Using this host-pathogen biomarker profile, we show that treatment outcome can be predicted before the start of treatment. These findings not only raise the possibility of point-of-care diagnostic screening to identify patients at high risk of treatment failure and provide a rationale for a precision medicine approach to drug selection in cutaneous leishmaniasis, but more broadly also demonstrate the value of identifying genes of high variability in other diseases to better understand and predict diverse clinical outcomes.

The locations of the core components of this repo are outlined in the file system map below. In short, there are the following main directories:

• /ANALYSIS/code - contains the Rmarkdown (.rmd) file that combines all code and outputs and was used to generate the supplementary code file included in the manuscript the pipeline. All code for manuscript figures based on RNAseq data are included in this document. Also contains the study design files that describe each sample.
• /ANALYSIS/readMapping/human - includes Kallisto outputs and log files for mapping of raw fastq files from Amorim et al., (this study) to the human reference transcriptome. This directory is listed in the .gitingore due to restrictions on file and repo size set by GitHub.
• /ANALYSIS/readMapping/Lbraz - Kallisto outputs and log files for mapping of de-hosted reads from Amorim et al. (this study) to the L. braziliensis reference transcriptome.
• /ANALYSIS/Christensen_plosNTD_2016/human - Kallisto outputs and log files for mapping of raw fastq files from Christensen et al., to the human reference transcriptome. This directory is listed in the .gitingore due to restrictions on file and repo size set by GitHub.
• /ANALYSIS/Christensen_plosNTD_2016/Lbraz - Kallisto outputs and log files for mapping of de-hosted reads from Christensen et al., to the L. braziliensis reference transcriptome
• /QA/fastqc_Amorim - includes outputs from running fastqc on all raw fastq files from Amorim et al. (this study).
• /QA/fastqc_Christensen - includes outputs from running fastqc on all raw fastq files from Christensen et al..
• /QA/multiqc_report_Amorim_host.html - multiqc html summary report that summarizes fastqc and kallisto results from mapping raw fastq files from Amorim et al., (this study) to the human reference transcriptome.
• /QA/multiqc_report_Amorim_parasite.html - multiqc html summary report that summarizes fastqc and kallisto results from mapping de-hosted reads from Amorim et al., (this study) to the L. braziliensis reference transcriptome.
• /QA/multiqc_report_Christensen_host.html - multiqc html summary report that summarizes fastqc and kallisto results from mapping raw fastq files from Christensen et al., to the human reference transcriptome.
• /QA/multiqc_report_Christensen_parasite.html - multiqc html summary report that summarizes fastqc and kallisto results from mapping de-hosted reads from Christensen et al., to the L. braziliensis reference transcriptome.