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Tsolakidis, K.

Publications and source records attributed to Tsolakidis, K..

2 recordsLinked to original sources

BioBrain: A Multi-Agent Framework for Natural Language Driven Quantitative Microscopy Data Analysis

Advances in fluorescence microscopy have dramatically expanded the range of biological questions that can be addressed, enabling quantitative observations of molecular interactions and cellular dynamics with unprecedented spatial and temporal resolution. However, the growing complexity of imaging data has outpaced our ability to analyze them. Despite numerous computational methods exist, they often rely on specialized software environments, heterogeneous data formats, and technical expertise, limiting adoption and widening the gap between data acquisition and quantitative biological interpretation. Here we introduce BioBrain, a multi-agent framework that translates natural-language analytical goals into executable and reproducible microscopy analysis pipelines. Instead of generating analysis code, BioBrain assembles validated analytical methods and can expands its analytical capabilities by integrating existing laboratory scripts into a unified conversational framework. Every selected method and inferred parameter is transparently reported, ensuring traceable and reproducible analyses. On two-channel total internal reflection fluorescence and three-dimensional lattice light-sheet benchmarks, BioBrain exactly reproduces expert-derived results when parameters are specified and degrades predictably and traceably when they are not, while frontier language models generated large, model-dependent quantitative errors despite completing without warning. BioBrain offers a practical path for closing the widening gap between data acquisition and biological discovery, enabling experimental scientists to communicate with computational analysis in the language of biology rather than the language of software.

biophysics↗

Rapid and reliable quantification of cytosolic mRNA escape (RNASCAPE)

Endosomal escape of mRNA remains a critical bottleneck in oligonucleotide therapeutics, with typically less than 5% of delivered mRNA reaching the cytosol. Precise quantification of this escape is hindered by stochastic variability in uptake, release, and expression, while existing methods lack scalability and accuracy. Here we introduce RNASCAPE, a deep learning framework trained on biologically realistic simulations that estimates unlabelled mRNA cytosolic escape efficiency using only three timepoints of EGFP reporter expression and four lipid nanoparticle (LNP) meta-parameters. Benchmarking on synthetic data shows RNASCAPE achieves a mean absolute percentage accuracy of 78%. RNASCAPE accurately predicts escape efficiencies around 5-9% across diverse cell types and revealed that exchanging cholesterol to {beta}-sitosterol drastically reduces mRNA loading and enhances twofold its functional release. By enabling robust, microscopy-agnostic quantification without requiring specialized cell lines or labeled cargo, RNASCAPE provides a scalable framework for benchmarking and rational design of LNP formulations, advancing nucleic acid therapeutic delivery.

biophysics↗