Orre, L. M. | bioRxiv Science

bioRxiv2026

Mass spectrometry-based proteomics delivers in-depth proteome profiling of FFPE lung cancer biopsies from single glass slides

Clinical proteomics has the potential to add a valuable data layer to genomic and histopathological analyses in precision oncology, but its application to limited clinical material remains challenging. Here, we demonstrate that state-of-the-art mass spectrometry-based proteomics enables in-depth proteomic profiling of formalin-fixed paraffin-embedded (FFPE), including small biopsies and single tissue sections mounted on glass slides. Despite minimal input material, single-slide analyses of clinical lung tumor specimens yielded biologically and clinically informative data, supporting detection of actionable proteins, immune-related signatures, and multivariate biomarkers. These results establish the feasibility of proteomics for retrospective FFPE studies and routine clinical practice, expanding opportunities for biomarker discovery and precision medicine from scarce tissue material.

cancer biology↗

bioRxiv2017

A small core set of transcription factors bind strongly to DNA in different cell types

It is well established that transcription factors (TFs) play crucial roles in determining cell identity, and that a large fraction of all TFs are expressed in most cell types. In order to globally characterize activities of TFs in cells, we have developed a novel massively parallel protein activity assay, Active TF Identification (ATI) that measures DNA-binding activity of all TFs from any species or tissue type. In contrast to previous studies based on mRNA expression or protein abundance, we found that a set of TFs binding to only around ten distinct motifs display strong DNA-binding activity in any given cell or tissue type. Mass spectrometric identification of TFs revealed that within these highly active TFs, there were both housekeeping TFs, which were universally found in all cell types, and specific TFs, which were highly enriched in known factors that determine the fate of the analyzed tissue or cell type. The importance of a small subset of TFs for determining the overall accessible chromatin landscape of a cell suggests that gene regulatory logic may be simpler than what has previously been appreciated.

cell biology↗