Stegle Lab
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steglelab.bsky.social
Stegle Lab
@steglelab.bsky.social
Our group develops and applies computational approaches to study molecular variations and their phenotypic consequence. We are part of DKFZ and EMBL.
Website: https://steglelab.org/
Contact us by email if you meet the eligibility criteria and are interested in applying based on our project outline. Your email should include your project proposal, a CV and two reference letters. We look forward to hearing from you.

Project Outline Nr. 58: drive.google.com/file/d/1YZbs...
Alliance_project-outline Stegle Krijgsveld.pdf
drive.google.com
January 20, 2026 at 9:43 AM
Important information:
- A minimum of one first-author publication is required
- Applicants must develop their own research proposal based on our project outline
- Provide your CV, two reference letters and your project proposal
- Expected start date: between August 1, 2026, and January 1, 2027
January 20, 2026 at 9:43 AM
SCP enables the quantification of thousands of proteins per individual cell, thereby revealing cell states, regulatory mechanisms, and functional heterogeneity. Join us in developing a framework to analyze comprehensive SCP datasets (up to 6000 quantified proteins per cell!).
January 20, 2026 at 9:43 AM
January 7, 2026 at 9:53 AM
We further describe how these methods achieve the 3 key aims of causal modelling:
1️⃣ Understand perturbation responses
2️⃣ Extrapolate to unseen conditions
3️⃣ Guide future experiments
January 7, 2026 at 9:53 AM
We map how these methods commonly utilise partial views of causal signatures (perturbations ⚡, temporal ⏳, spatial 📍& multi-omics 🧬) and rely on a shared core modelling concepts (from Disentanglement to Mechanistic Discovery).
January 7, 2026 at 9:53 AM
Explore the tools covered in our review in an online repository: interp-extrap-perturb.readthedocs.io 💻
This database is continuously growing, and we invite everyone to submit methods and help us keep the repository up-to-date.
Interpretation, Extrapolation, and Perturbation of Single Cells — Interpretation, Extrapolation, and Perturbation of Single cells
interp-extrap-perturb.readthedocs.io
January 7, 2026 at 9:53 AM
We review and connect >150 methods to help you choose the most suitable method for a given biological task and dataset.
Our perspective further proposes a unifying ontology to structure and organise these methods across tasks, assumptions, and modelling concepts.
January 7, 2026 at 9:53 AM
scPT-seq directly links genotype, expression, lineage & space in vivo. A powerful framework for functional genomics beyond indirect CRISPR readouts. 9/10
December 27, 2025 at 4:13 PM
CRISPR edits also act as heritable clonal markers.
We reconstruct lineages, transfer spatial information between cells, and uncover region-specific stem cell identities and perturbation responses. 8/10
December 27, 2025 at 4:13 PM
scPT-seq also enables dosage-dependent analysis:
Different cell types respond differently to mono- vs biallelic mutations, revealing spatially organized compensatory mechanisms across the tissue. 7/10
December 27, 2025 at 4:13 PM
Key insight:
Standard perturbed-vs-control comparisons are dominated by stress responses.
Using true internal WT cells, scPT-seq uncovers mutation-specific transcriptional programs that were previously hidden. 6/10
December 27, 2025 at 4:13 PM
We applied scPT-seq to the Drosophila midgut, a regenerative tissue with strong spatial structure.
This lets us compare mutant and wild-type cells within the same tissue, separating genetic from environmental effects. 5/10
December 27, 2025 at 4:13 PM
What do we gain?
1️⃣ Base-pair resolution of CRISPR edits
2️⃣ Detection of insertions, deletions and splice changes
3️⃣ Clear distinction between WT, mono- and biallelic edits
4️⃣ Identification of “missing” alleles (a major blind spot of past methods) 4/10
December 27, 2025 at 4:13 PM
scPT-seq combines:
• droplet-based scRNA-seq
• targeted long-read sequencing of edited loci
• haplotype-resolved mutation calling
All from the same cells, in vivo. 3/10
December 27, 2025 at 4:13 PM
The problem:
Guide capture ≠ successful edit.
Computational inference ≠ true genotype.
And in vivo, environmental effects easily mask real mutation-driven responses.
So how do we truly link genotype to phenotype at single-cell resolution? 2/10
December 27, 2025 at 4:13 PM
You’ll help build interoperable, FAIR tools across @scverse.bsky.social and @bioconductor.bsky.social ecosystems. You will work together with a cross-institute team composed of @lucamarconato.bsky.social, @arturmansl.bsky.social and many contributors from #scverse and #Bioconductor!
December 27, 2025 at 3:50 PM