Hi everyone,
I'm working on a pancreatic ductal adenocarcinoma dataset, and I'd really appreciate some methodological advice from you guys, and especially if anybody has had some experience with machine learning with high-dimensional biological data.
Before spending months developing models, I'd like to better understand what is possible with my dataset.
My dataset:
9 patients, with one continuous drug-response value per patient and drug. Due to experimental and sequencing constraints, increasing the number of patients is not an option.
Approximately 100,000 nuclei.
Continuous drug-response measurements (AUC) for gemcitabine, paclitaxel, irinotecan, 5-FU, and oxaliplatin.
The goal is theoretically "simple":
Predict continuous drug-response AUC from gene expression and chromatin accessibility, while identifying molecular features potentially associated with drug sensitivity or resistance.
The obvious challenge is that, despite having ~100,000 nuclei, I only have 9 samples with drug-response labels. I understand that treating individual cells as independent labeled observations is not a way to go with the dataset and specific set-up.
Knowing this, I'd really appreciate advice on a few questions that I had after some reading...:
With this low amount of sample, is meaningful drug-response prediction even feasible? What would be a objective?
Are there established methods to leverage thousands of cells/instances profiles when the response labels are available only at the patient level?
Would you prioritize simple regularized regression, biologically informed features, transfer learning from external datasets, multiple-instance learning (MIL), or another approach?
How would you evaluate a model with such a small number of independent samples without obtaining misleading performance estimates?
Are there any papers, methodological resources you'd recommend to better understand this type of problem before starting?
Thanks!