Biology subjects

Schäfer, P. S. L.

Publications and source records attributed to Schäfer, P. S. L..

4 recordsLinked to original sources

bioRxiv2026

Towards Principled Evaluation of Single-Cell Perturbation Prediction Models

Single-cell perturbation experiments measure how interventions alter cellular phenotypes. However, the number of possible perturbations and biological contexts far exceeds what can be tested experimentally. Motivated by this constraint, predictive models aim to extrapolate cellular responses to unseen conditions. Despite substantial efforts in model development, benchmark studies have reached inconsistent conclusions about the capabilities of current perturbation-response models. A major challenge is that evaluation protocols vary widely across studies, making results difficult to compare. Furthermore, the lack of consensus on evaluation hampers progress because it is unclear which predictive capabilities new models should prioritize. To help build consensus on evaluation principles, we develop a taxonomy that decomposes evaluation protocols into their representation, metric, score transformation, and reporting strategies. We characterize how these choices determine which aspects of prediction quality a benchmark measures and discuss criteria for selecting and assessing protocols in relation to specific benchmarking goals. We additionally provide scPertEval, a Python package with reference implementations of selected evaluation protocols, and use it to assess protocol behavior across seven publicly available single-cell perturbation datasets. By making evaluation choices and their underlying trade-offs explicit, we aim to stimulate a community discussion about developing more comparable and task-aligned evaluation protocols. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/740433v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@bd1e3corg.highwire.dtl.DTLVardef@c26c2org.highwire.dtl.DTLVardef@1c49afdorg.highwire.dtl.DTLVardef@9b988c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

A transcriptional patient map of systemic lupus erythematosus reveals disease-related multicellular immune programs conserved between blood and kidney

Systemic lupus erythematosus (SLE) shows marked clinical and molecular heterogeneity, yet patient stratification often relies on gene expression signatures lacking multicellular context. Here we construct a transcriptional patient map of SLE by analyzing 1,167 total samples (783 SLE, 384 healthy controls) across different resolutions, including single-cell and bulk blood as well as spatially resolved kidney tissue transcriptomes. Using an unsupervised approach we inferred patient-level transcriptomic immune programs from two independent single-cell RNA sequencing cohorts of peripheral blood mononuclear cells (PBMCs), capturing both differences between SLE and health as well as within-SLE heterogeneity. Specifically, we identified four conserved programs comprising two multicellular inflammatory programs driven by interferon and TNF/NFkB activity across immune cells, and two cell type-specific programs reflecting CD8 T cell cytotoxicity and a CD4 T cell naive-to-effector state. Functional analysis of these programs revealed a rewiring of both cell-to-cell interactions and task allocation across cell types during disease activation. In addition, mapping these programs onto an external longitudinal blood transcriptomic cohort predicted flare risk and identified candidate blood protein biomarkers detectable by proteomics. Finally, we showed that these blood programs were enriched in immune-infiltrated glomerular regions from kidney biopsies of individuals with lupus nephritis using spatially resolved transcriptomic data, thereby linking systemic immune programs to local tissue pathology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/721379v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1e75f00org.highwire.dtl.DTLVardef@10e0a63org.highwire.dtl.DTLVardef@cc194forg.highwire.dtl.DTLVardef@191b4d2_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

ParTIpy: A Scalable Framework for Archetypal Analysis and Pareto Task Inference

MotivationTrade-offs between different functions or tasks are pervasive across scales in biological systems. For example, individual cells cannot perform all possible functions simultaneously; instead they allocate limited resources to specialize in subsets of tasks by activating specific gene expression programs. Pareto Task Inference (ParTI) is a framework for analyzing biological trade-offs grounded in the theory of multi-objective optimality. However, existing software implementations of ParTI lack scalability to large datasets and do not integrate well with standard biological data analysis workflows, especially in the context of single-cell transcriptomics, limiting broader adoption. ResultsWe have developed ParTIpy (Pareto Task Inference in Python), an open-source Python package that combines advances in optimization and coreset methods to scale archetypal analysis, the primary algorithm underlying ParTI, to large-scale datasets. By providing additional tools to characterize archetypes, comprehensive documentation, and adopting standard scverse data structures, ParTIpy facilitates seamless integration into existing analysis workflows and broadens accessibility, particularly within the single-cell community. We demonstrate how ParTIpy can be used to study intra-cell-type gene expression variability through the lens of task allocation, offering a principled alternative to methods that impose discrete cell state classifications on inherently continuous variation. Availability and implementationParTIpys open-source code is available on GitHub (https://github.com/saezlab/ParTIpy) and pypi (https://pypi.org/project/partipy). Documentation is available at https://partipy.readthedocs.io. The code to reproduce the results of this paper is on GitHub (https://github.com/saezlab/ParTIpy_paper)

bioinformatics↗

bioRxiv2023

LIANA+: an all-in-one cell-cell communication framework

The growing availability of single-cell and spatially-resolved transcriptomics has led to the rapidly growing popularity of methods to infer cell-cell communication. Many approaches have emerged, each capturing only a partial view of the complex landscape of cell-cell communication. Here, we present LIANA+, a scalable framework to decode coordinated inter- and intracellular signalling events from single- and multi-condition datasets in both single-cell and spatially-resolved data. Beyond integrating and extending established methodologies and a rich knowledge base, LIANA+ enables novel analyses using diverse molecular mediators, including those measured in multi-omics data. Accessible as an open-source Python package at https://github.com/saezlab/liana-py, LIANA+ provides a comprehensive set of synergistic components to study cell-cell communication. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/553863v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@16486ceorg.highwire.dtl.DTLVardef@ce6821org.highwire.dtl.DTLVardef@1165e54org.highwire.dtl.DTLVardef@18add5a_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗