Fabian J. Theis

AlphaPeptTools: scverse-native analysis of mass spectrometry-based proteomics

Mass spectrometry (MS)-based proteomics now routinely profiles proteomes at scale, but extracting biological insight and integrating complementary modalities remains challenging. Here, we present AlphaPeptTools, a Python package for the analysis of MS-proteomics data built on the AnnData data structure of the scverse....

SPARCS enables scalable recovery of complex image-based phenotypes for genetic screening.

Forward genetic screening links genotype to phenotype by introducing random genetic perturbations and identifying phenotype-altering mutations. Although genome-scale screens are routine for simple phenotypes in cultured cells, extending them to complex image-based phenotypes remains challenging. Here, we present spatia...

MAFA drives pancreatic islet maturation through coordination of cell growth, metabolic maturation, and resilience to stress

A Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease

Multimodal discovery of a pathogenic B cell-dependent T cell state in multiple sclerosis.

B cell depleting therapies in multiple sclerosis (MS) have transformed disease management, yet the immunological mechanisms linking B cells to chronic compartmentalised CNS inflammation, the key pathological driver of disability accrual, remain poorly defined. Here, we leverage anti-CD20 therapy as an in vivo perturbat...

Designing antimicrobials with programmable mechanism and safety

OmegAMP, a conditional diffusion framework controlling net charge, mean hydrophobicity, and sequence length, supporting de novo, analog, and motif-guided design, opens a programmable route to new peptide antibiotics whose mechanism and safety follow from the chosen prototype.

Multi-scale modeling of human tissues from spatial transcriptomics with TERRA

Spatial transcriptomics maps gene expression at cellular resolution, revealing how cells organize into multicellular niches. Yet computational analyses remain dataset-specific, without a transferable representation of tissue organization that generalizes across datasets, tasks and tissues or predicts how tissues behave...

Learning Discrete Cell and Niche Codes from Spatial Transcriptomics Using Dual Residual Vector Quantization

SQUINT is presented, a graph vector-quantized variational autoencoder that learns two disjoint codebooks per cell from a shared architecture that outperforms or is competitive with strong baselines on identification and achieves the most faithful cross-section integration.

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies.

This work demonstrates how proteins created by generative artificial intelligence can be harnessed for the rational engineering of RNA transport systems with the desired properties by overcoming the limitations of natural protein diversity.

Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer’s disease

It is shown that a disease-associated microglial subtype, characterized by elevated GPNMB expression and enriched for polygenic AD risk, expands with AD pathology and shows increased phagocytic activity, and MITF is identified as an upstream regulator required to maintain this microglial state.

A multimodal interrogation of Broca’s area in the pediatric and adult human brain

Language is a defining trait of our species, and disruptions in language acquisition can have profound consequences to the individuals affected. Uncovering the neurodevelopmental basis of this complex trait requires detailed molecular and cellular insights into the neocortical areas that support linguistic abilities. H...