Merge pull request #59 from matsengrp/process-chen-pa-dms

Process Chen et al. PA DMS data and integrate into pipeline

Author: Haddox

README.md

@@ -237,6 +237,13 @@ Processes raw deep mutational scanning (DMS) data from external sources into sta
 2. Aligns the DMS NEP sequence (PR8 strain) to the reference using MUSCLE; uses actual DMS site numbers for coordinate mapping to handle non-consecutive site numbering
 3. Outputs `results/dms_data/Teo_NEP/processed_dms_data.csv` — NEP DMS data with tree reference site numbering
 
+**`process_dms_data_chen_pa.ipynb`** (Chen et al., PA):
+1. Parses the AA mutation column to extract wildtype AA, DMS site, and mutant AA; excludes indel and stop codon mutations
+2. Averages the two no-drug fitness replicates (P1NO-1-fit, P1NO-2-fit) and groups by AA mutation (multiple nucleotide changes can produce the same AA change)
+3. Computes log-scale DMS effects: `log(mean fitness without drug)`
+4. Aligns the DMS sequence (first 240 AA of PA) to the PA tree reference using MUSCLE to establish site numbering correspondence
+5. Outputs `results/dms_data/Chen_PA/processed_dms_data.csv` — PA DMS data with tree reference site numbering
+
 ### Step 11: Analyze Site-Specific Rates
 
 Executes an analysis notebook that:
@@ -450,6 +457,7 @@ Located in the `results/` root directory:
    - `Li_PB1/processed_dms_data.csv` - PB1 DMS fitness effects (Li et al. 2023) with tree reference site numbering
    - `Hom_M1/processed_dms_data.csv` - M1 DMS fitness effects (Hom et al. 2019) with tree reference site numbering
    - `Teo_NEP/processed_dms_data.csv` - NEP DMS fitness effects (Teo et al. 2024) with tree reference site numbering
+   - `Chen_PA/processed_dms_data.csv` - PA DMS fitness effects (Chen et al. 2024) for first 240 AA with tree reference site numbering
 
 ### Output Structure Example
 
@@ -494,7 +502,9 @@ results/
 │   │   └── processed_dms_data.csv
 │   ├── Hom_M1/
 │   │   └── processed_dms_data.csv
-│   └── Teo_NEP/
+│   ├── Teo_NEP/
+│   │   └── processed_dms_data.csv
+│   └── Chen_PA/
 │       └── processed_dms_data.csv
 ├── .process_dms_data_soh_pb2.done
 ├── .summarize_filter_logs.done

Snakefile

@@ -116,6 +116,7 @@ final_outputs.extend([
     f"{config['output_dir']}/dms_data/Li_PB1/processed_dms_data.csv",
     f"{config['output_dir']}/dms_data/Hom_M1/processed_dms_data.csv",
     f"{config['output_dir']}/dms_data/Teo_NEP/processed_dms_data.csv",
+    f"{config['output_dir']}/dms_data/Chen_PA/processed_dms_data.csv",
 ])
 
 # Add analyze_fitness_effects to final targets
@@ -487,6 +488,28 @@ rule process_dms_data_teo_nep:
             -p data_dir $data_dir &> ../{log}
         """
 
+# Process PA DMS data from Chen et al.
+rule process_dms_data_chen_pa:
+    input:
+        notebook="notebooks/process_dms_data_chen_pa.ipynb",
+        pa_data="data/dms_data/Chen_PA/fitness calculation.xlsx"
+    output:
+        pa_dms="{output_dir}/dms_data/Chen_PA/processed_dms_data.csv"
+    params:
+        data_dir=config["data_dir"]
+    log:
+        "{output_dir}/logs/process_dms_data_chen_pa.log"
+    shell:
+        """
+        data_dir=$(realpath {params.data_dir}) && \
+        cd notebooks && \
+        papermill \
+            process_dms_data_chen_pa.ipynb \
+            process_dms_data_chen_pa.ipynb \
+            -p data_dir $data_dir &> ../{log}
+        """
+
+
 # Analyze fitness effects and compare to DMS data
 rule analyze_fitness_effects:
     input:
@@ -499,7 +522,8 @@ rule analyze_fitness_effects:
         na_dms="{output_dir}/dms_data/Wang_NA/processed_dms_data.csv",
         pb1_dms="{output_dir}/dms_data/Li_PB1/processed_dms_data.csv",
         m1_dms="{output_dir}/dms_data/Hom_M1/processed_dms_data.csv",
-        nep_dms="{output_dir}/dms_data/Teo_NEP/processed_dms_data.csv"
+        nep_dms="{output_dir}/dms_data/Teo_NEP/processed_dms_data.csv",
+        pa_dms="{output_dir}/dms_data/Chen_PA/processed_dms_data.csv"
     output:
         touch("{output_dir}/.analyze_fitness_effects.done")
     log: