scOPE — single-cell Oncological Prediction Explorer

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scOPE workflow (transfer learning from bulk → single-cell)

scOPE is a transfer-learning framework that uses bulk RNA-seq cohorts with known mutation status to learn a compact, biologically meaningful latent space, then projects single-cell RNA-seq into that same space to predict the probability that specific cancer-associated gene mutations are present in individual cells. This provides mutation-informed subclonal structure that can complement CNV methods and increase subclonal granularity.

Overview

scOPE proceeds in two phases:

1) Learn latent factors from bulk RNA-seq and train mutation classifiers (Panels a–c)

• i. Bulk expression matrix
  Construct a bulk cohort expression matrix A_bulk (rows = patient samples, columns = genes).
  The bulk matrix is normalized / centered / scaled to ensure comparable gene-wise signal.

• ii. Latent feature mapping via SVD
  Decompose the normalized bulk matrix using SVD:

  

  • U_bulk: sample scores (rows = patients, columns = latent factors)
  • Σ_bulk: diagonal matrix of singular values
  • V: gene loadings (rows = genes, columns = latent factors)

  Define the bulk latent representation (patient-by-factor embedding):

  

• iii. Train mutation-prediction models in latent space
  For each mutation / gene-of-interest, train a supervised ML model to predict mutation presence Y from Z_bulk.
  This yields one (or multiple) mutation-specific classifiers operating on the learned latent factors.

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2) Project scRNA-seq into the bulk-derived latent space and predict mutations per cell (Panels d–f)

• i. Single-cell expression matrix
  Construct a single-cell expression matrix A_sc (rows = single cells, columns = genes).

• ii. Normalize scRNA-seq using bulk-derived parameters
  Apply the same gene-wise normalization / centering / scaling learned from the bulk cohort to obtain A′_sc.
  (This alignment step makes the projection comparable across bulk and single-cell.)

• iii. Project cells into latent space and infer mutation probabilities
  Use the bulk-derived gene loadings V to compute the single-cell latent representation:

  

  Then apply the trained bulk models to Z_sc to predict per-cell mutation probabilities, producing mutation-informed cellular maps that can be analyzed alongside expression programs, clusters, and CNV signals.

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Installation

From PyPI

pip install scope-bio

With optional dependencies (UMAP, XGBoost, LightGBM, SHAP)

pip install scope-bio[full]

From conda-forge

conda install -c conda-forge scope-bio

Development install

git clone https://github.com/Ashford-A/scOPE.git
cd scOPE
conda env create -f environments/scope-dev.yml
conda activate scope-dev
pip install -e ".[dev]"

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Quick start

import anndata as ad
import pandas as pd
from scope import BulkPipeline, SingleCellPipeline
from scope.io import load_mutation_labels

# --- Phase 1: Bulk --------------------------------------------------------
adata_bulk = ad.read_h5ad("bulk_cohort.h5ad")
mutation_labels = load_mutation_labels("mutations.csv", sample_col="sample_id")

bulk_pipe = BulkPipeline(
    norm_method="cpm",
    decomposition="svd",   # "svd" | "nmf" | "ica" | "pca"
    n_components=50,
    classifier="logistic", # "logistic" | "random_forest" | "gbm" | "xgboost" | "lightgbm" | "svm" | "mlp"
)
bulk_pipe.fit(adata_bulk, mutation_labels, cv=5)
bulk_pipe.save("models/bulk_pipeline.pkl")

# --- Phase 2: Single cell --------------------------------------------------
adata_sc = ad.read_h5ad("sc_tumor.h5ad")

# Prepare a preprocessed bulk reference for moment matching
adata_bulk_pp = bulk_pipe.preprocessor_.transform(adata_bulk)

sc_pipe = SingleCellPipeline(
    bulk_pipeline=bulk_pipe,
    alignment_method="z_score_bulk",  # "z_score_bulk" | "moment_matching" | "quantile" | "none"
)
sc_pipe.fit(adata_bulk_pp, adata_sc)
adata_sc = sc_pipe.transform(adata_sc)

# adata_sc.obs now contains columns: mutation_prob_KRAS, mutation_prob_TP53, ...

# --- Visualise -------------------------------------------------------------
from scope.visualization import compute_umap, plot_mutation_probabilities

adata_sc = compute_umap(adata_sc, obsm_key="X_svd")
fig = plot_mutation_probabilities(adata_sc, mutations=["KRAS", "TP53"])
fig.savefig("mutation_probs.pdf", bbox_inches="tight")

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API reference

Preprocessing

Class	Description
BulkNormalizer	CPM / TPM / median-ratio / TMM normalisation
BulkScaler	Gene-wise centering and scaling
BulkPreprocessor	Combined normalise + scale
SingleCellPreprocessor	QC filter + normalise + optional scale
BulkSCAligner	z-score / moment-matching / quantile alignment

Decomposition

Class	Description
SVDDecomposition	Truncated SVD (randomized / ARPACK / full)
NMFDecomposition	Non-negative matrix factorization
ICADecomposition	FastICA
PCADecomposition	PCA via sklearn
get_decomposition(name)	Factory function

Classification

Class	Description
LogisticMutationClassifier	L1/L2/ElasticNet logistic regression
RandomForestMutationClassifier	Random forest
GBMMutationClassifier	Gradient boosting (sklearn)
XGBMutationClassifier	XGBoost
LGBMMutationClassifier	LightGBM
SVMMutationClassifier	SVM + Platt calibration
MLPMutationClassifier	Multi-layer perceptron
PerMutationClassifierSet	Trains/stores one classifier per mutation
get_classifier(name)	Factory function

Evaluation

Function	Description
evaluate_classifier	AUROC, AUPRC, Brier score
evaluate_all	Evaluate all mutations at once
cross_validate_classifiers	Stratified k-fold CV
roc_curve_data / pr_curve_data	Curve arrays for plotting

Visualization

Function	Description
compute_umap	UMAP on latent embedding
compute_tsne	t-SNE on latent embedding
plot_embedding	Scatter by categorical or continuous
plot_mutation_probabilities	Grid of per-mutation probability overlays
plot_scree	Singular value / EVR scree plot
plot_mutation_heatmap	Mean probability per cluster heatmap

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Running tests

pytest tests/ -v --cov=scope --cov-report=term-missing

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Citation

If you use scOPE in your research, please cite:

Ashford, A. et al. (2024). scOPE: transfer-learning from bulk RNA-seq to infer per-cell mutation probabilities in single-cell transcriptomics. [Journal] doi: ...

(Work currently in progress - will be filled out later once preprint is up on bioRxiv)

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License

MIT — see LICENSE.