Christoph Bock Lab @ CeMM & MedUni Vienna
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bocklab.bsky.social
Christoph Bock Lab @ CeMM & MedUni Vienna
@bocklab.bsky.social
Technology-driven biomedical research at CeMM Research Center for Molecular Medicine & MedUni Vienna #cancer #immunology #bioinformatics #AI #singlecell #CRISPR
🧬 CellWhisperer introduces a chat-based way to explore scRNA-seq data. By enabling natural language analysis, it bridges biologists and bioinformaticians—paving the way for AI-driven bioinformatics assistants. (10/11)
November 11, 2025 at 12:52 PM
📚 We trained on >1 million bulk & pseudo-bulk transcriptomes with textual annotations that we AI-curated from GEO & @CELLxGENE Census. Our training data is open source and useful for developing multimodal biomedical AI models and future bioinformatics research assistants. (8/11)
November 11, 2025 at 12:52 PM
🪄 How does CellWhisperer work behind the scenes? We trained a multimodal AI that links transcriptomes and text, enabling free-text search and annotation of RNA profiles. And we connected this model to an LLM that we fine-tuned into a chat assistant for transcriptome data (7/11)
November 11, 2025 at 12:52 PM
🚀 We also validated CellWhisperer’s chat-based analysis with conventional bioinformatics. CellWhisperer was >4x faster (and 10x cooler 😊). Our recommendation: Use CellWhisperer for dataset exploration – but statistics is still important to ensure rigor & reproducibility (6/11)
November 11, 2025 at 12:52 PM
🆕 The CellWhisperer paper (doi.org/10.1038/s415...) includes several new analyses beyond our 2024 bioRxiv preprint (biorxiv.org/content/10.1...). For example, we used CellWhisperer for an AI-guided analysis of human organ development (5/11)
November 11, 2025 at 12:52 PM
🔬 You can easily query large transcriptome datasets for your favorite biological process using CellWhisperer. Just open Tabula Sapiens (cellwhisperer.cemm.at/tabulasapiens/) or GEO (cellwhisperer.cemm.at/geo/) in CellWhisperer & type your query into the chat box – for example “infection” (4/11)
November 11, 2025 at 12:52 PM
🔍 We investigate one of the identified cell clusters by selecting the cells & prompting CellWhisperer with ‘Describe these cells in detail’. This interactive workflow is enabled by seamless integration of the CellWhisperer AI chat box into a version of CELLxGENE Explorer (3/11)
November 11, 2025 at 12:52 PM
⚙️ To get started, let’s find cells by typing into the CellWhisperer chat box. For example ‘Show me structural cells with immune functions’. CellWhisperer scores each transcriptome by how well it matches this textual query and colors by query match (red: high, blue: low) (2/11)
November 11, 2025 at 12:52 PM
🗨️ Just published in Nature Biotechnology: Our CellWhisperer AI enables chat-based analysis of single-cell sequencing data. You can talk to your cells & figure out the biology without writing any computer code. Paper here: www.nature.com/articles/s41.... Annotated walkthrough in a thread below (1/11)
November 11, 2025 at 12:52 PM
📚 We trained on >1 million bulk & pseudo-bulk transcriptomes with textual annotations that we AI-curated from GEO & CELLxGENE Census. Our training data is open source and useful for developing multimodal biomedical AI models and future bioinformatics research assistants. (8/11)
November 11, 2025 at 12:41 PM
🪄 How does CellWhisperer work behind the scenes? We trained a multimodal AI that links transcriptomes and text, enabling free-text search and annotation of RNA profiles. And we connected this model to an LLM that we fine-tuned into a chat assistant for transcriptome data (7/11)
November 11, 2025 at 12:41 PM
🚀 We also validated CellWhisperer’s chat-based analysis with conventional bioinformatics. CellWhisperer was >4x faster (and 10x cooler 😊). Our recommendation: Use CellWhisperer for dataset exploration – but statistics is still important to ensure rigor & reproducibility (6/11)
November 11, 2025 at 12:41 PM
🆕 The CellWhisperer paper (doi.org/10.1038/s415...) includes several new analyses beyond our 2024 bioRxiv preprint (biorxiv.org/content/10.1...). For example, we used CellWhisperer for an AI-guided analysis of human organ development (5/11)
November 11, 2025 at 12:41 PM
🔬 You can easily query large transcriptome datasets for your favorite biological process using CellWhisperer. Just open Tabula Sapiens (cellwhisperer.cemm.at/tabulasapiens/) or GEO (cellwhisperer.cemm.at/geo/) in CellWhisperer & type your query into the chat box – for example “infection” (4/11)
November 11, 2025 at 12:41 PM
🔍 We investigate one of the identified cell clusters by selecting the cells & prompting CellWhisperer with ‘Describe these cells in detail’. This interactive workflow is enabled by seamless integration of the CellWhisperer AI chat box into a version of CELLxGENE Explorer (3/11)
November 11, 2025 at 12:41 PM
⚙️ To get started, let’s find cells by typing into the CellWhisperer chat box. For example ‘Show me structural cells with immune functions’. CellWhisperer scores each transcriptome by how well it matches this textual query and colors by query match (red: high, blue: low) (2/11)
November 11, 2025 at 12:41 PM
⚕️ Our CELLFIE platform supports clinical translation of CRISPR-boosted CAR T cells. For example, to avoid the DNA double-strand breaks introduced by CRISPR knockout, we performed a tiling base-editing screen across RHOG and identified promising gRNA for clinical testing. (11/13)
September 24, 2025 at 6:42 PM
🔥 What’s next? Our discovery of strong combined effects for RHOG & FAS knockout underlines the potential of synergistic gene edits for boosting CAR T cell function. We thus integrated combinatorial screening into CELLFIE, using the Blainey lab’s CROPseq-multi method. (10/13)
September 24, 2025 at 6:42 PM
🔬 From a technical perspective, we are excited how our new in vivo CROP-seq method improves gRNA detection (reading from an mRNA transcript as in nature.com/articles/nme...) and reduces experimental noise (by using UMIs), which enables larger screens with fewer mice. (9/13)
September 24, 2025 at 6:42 PM
💪 We also observed prolonged survival for FAS knockout CAR T cells, likely because these cells are less effective at killing each other (“fratricide”). Combining RHOG & FAS knockout, we obtained more & better CAR T cells, which further improved survival in leukemic mice. (8/13)
September 24, 2025 at 6:42 PM
🔍 RHOG is a small GTPase involved in cell signaling. How does it influence CAR T cells ? We found that RHOG knockout increases the proliferative capacity of CAR T cells and helps them retain a highly functional state with reduced exhaustion and enhanced memory phenotype. (7/13)
September 24, 2025 at 6:42 PM
🐁 We performed extensive in vivo validations and found that RHOG knockout CAR T cells achieve strong reductions in cancer cell numbers and prolonged survival in an aggressive mouse model of human leukemia, with consistent results across different CARs and T cell donors. (6/13)
September 24, 2025 at 6:42 PM
🐭 But not everything that makes CAR T cells proliferate or kill better in vitro translates into more effective therapies. For scalable validation in mice, we conducted pooled in vivo CRISPR screening and observed strong positive effects of RHOG, PRDM1, and FAS knockouts. (5/13)
September 24, 2025 at 6:42 PM
🩸 Using CELLFIE, we conducted 58 genome-wide CRISPR screens, with readouts for CAR T cell proliferation, target cell recognition, activation, apoptosis & fratricide, and exhaustion. The screens identified known genes (PD-1, CTLA4, TIM3, TIGIT etc.) and promising new hits. (3/13)
September 24, 2025 at 6:42 PM
⚙️ We developed CELLFIE (“cell engineering for immunotherapy enhancement”), a CRISPR platform to make & test gene-edited CAR T cells at scale. CELLFIE supports in vitro & in vivo screens with various clinically relevant readouts, plus combinatorial & base-editing screens. (2/13)
September 24, 2025 at 6:42 PM