title	author	date
InflaMix	Sandeep Raj	2023-07-08

InflaMix Manuscript Code

This github repository contains code and models that accompany the InflaMix manuscript while it is under review.

After publication, this git will be updated with:

• a link to the paper
• guidance on how to use InflaMix
• additional code to further facilitate direct implementation of InflaMix for research with new data sets

A description of the two data inputs for this project and a description of their column values is given in the comments at the beginning of scaling_sfig3.R.

Scripts should be run in the following order which contains code for the corresponding figures:

Set-up

1. Download this entire directory from GitHub. Open the "InflaMix.Rproj" file in a suitable IDE like R-Studio.

2. Install all required packages, either manually by reviewing required libraries at the top of every script in the "scripts/" directory, or use the "renv" package "https://rstudio.github.io/renv/articles/renv.html"

• Note that the "survcomp" and "ComplexHeatmap" packages require installation through BioConductor.
• https://bioconductor.org/packages/release/bioc/html/survcomp.html
• https://bioconductor.org/packages/release/bioc/html/ComplexHeatmap.html
• Download and Installation should not more than a few minutes to an hour.

3. Follow the steps below.

0 . Please place Dataset 1 (deriv_cohort_d0_labs_v2_dataset1.csv) into the data folder. This was provided as a supplementary material.

Every script here should run within a minute. There are two exceptions (see steps 5 and 7)

1. scaling_sfig3.R

• Supplementary Figure 3

2. modelgen_efig2h_i.R

• Extended Figure 2h, i

3. icl_bic_efig2a.R

• Extended Figure 2a

4. efig2b_g.R

• Extended Figure 2b-g

5. deriv_cohort_properties_fig1a_g_sfig2.R

• Figure 1a-g, Supplementary Figure 2
• Note that Figures 1d, e, f cannot be plotted with provided data, code should be run line-by-line.
• In generating Figure 1g, the run time for generating each independent iteration of random forest will take 3-5 minutes. For 100 iterations this will take several hours.

6. deriv_outcomes_fig1h_l_table2.R

• Figure 1h-l
• Note that this script cannot be run with provided data.

7. partial_lab_clustering_fig2ab_fig2a_c.R

• Figure 2a-b, Figure 3a-c
• Note that this script cannot be run with provided data. Though the code and comments describe the analysis to evaluate the quality of clustering with partially available laboratory data
• In assigning clusters to patients with randomly simulated missing data over 100 iterations and evaluating pairwise linear regressions across iterations, the run time for this script will take ~2-3 hours.

8. validation_fig2c_k_fig3d_l_efig4_table2.R

• Figure 2c-k, Figure 3d-l, Extended Figure 4a-f
• Note that this script cannot be run with provided data.

9. cohort_heatmaps_efig3a_d.R

• Extended Figure 3a-d
• Note that only Extended Figure 3a be plotted with provided data

10. exploratory_analyses_MTV_table2.R

• Note that this script cannot be run with provided data.

11. cluster_transitions_figure6a_e.R

• Figure 6a-e
• Note that this script cannot be run with provided data.

Packages and version information for most dependencies are included in the renv.lock lockfile. All required libraries are listed at the top of each script.

The InflaMix model features are in the "model" directory.

Data availability

Data requests for patient-related laboratory measurements or clinical outcomes will be reviewed by the corresponding author in consultation with coauthors from Hackensack University Medical Center and Sheba Medical Center. Any data and materials that can be shared will be released via data transfer agreement. Laboratory values and their corresponding upper limits of normal for the model-derivation cohort of MSK patients are provided in the Supplementary Data (Data Set 1). With this data, the following figures can be reproduced:

• Figure 1 a-c, g
• Extended Figure 2 a-i
• Extended Figure 3 a
• Supplementary Figure 2
• Supplementary Figure 3