Global profiling of the proteome and acetylome in mice with abdominal aortic aneurysms

Yang, J.; Zhang, L.; Yang, B.; Ding, T.; Zhao, Y.; Yang, Y.; Tang, X.; Wu, Y.; Wang, Q.; Zhang, Z.; Shi, C.; Han, R.; Zhang, X.; Liu, J.

doi:10.1101/2025.06.02.657536

bioRxiv · 10.1101/2025.06.02.657536

Global profiling of the proteome and acetylome in mice with abdominal aortic aneurysms

Yang, J.·Zhang, L.·Yang, B.·Ding, T.·Zhao, Y.·Yang, Y.·Tang, X.·Wu, Y.·Wang, Q.·Zhang, Z.·Shi, C.·Han, R.·Zhang, X.·Liu, J.

View original source ↗Export metadata ↓

Abstract

BackgroundAbdominal Aortic Aneurysm (AAA) is a life-threatening vascular condition characterized by a progressive dilation of the abdominal aorta and a high risk of rupture. Currently, no effective pharmacological therapies are available, and treatment relies mainly on surgical intervention. The lack of drug targets is largely due to limited understanding of the molecular mechanisms underlying AAA development. This study aims to identify potential therapeutic targets by performing comprehensive proteomic and acetylomic analyses in a mouse model of AAA. MethodsWe conducted global proteomic and acetylomic profiling on abdominal aortic tissues collected from an AAA mouse model. A total of 7,858 proteins and 1,790 acetylated proteins encompassing 4,581 acetylation sites were quantified. Bioinformatics analyses were performed to investigate the regulatory networks and biological pathways associated with these proteins and post-translational modifications. ResultsIntegrated analysis revealed that histone-related proteins were significantly enriched in pathways co-regulated by the proteome and acetylome. These pathways are influenced by histone acetyltransferases and deacetylases, implicating histone acetylation in AAA-related inflammatory and immune processes. Notably, the deacetylases Sirt2 and Sirt5 were identified as potential regulators of neutrophil extracellular trap (NET) formation through suppression of histone acetylation. ConclusionsThis study provides the first comprehensive proteomic and acetylomic dataset for abdominal aortic tissues in a mouse model of AAA, substantially expanding the mouse acetylation database. The results highlight the central role of histone modifications in immune dysregulation and inflammation, and propose Sirt2 and Sirt5 as candidate therapeutic targets that may inhibit NET formation and slow AAA progression. These findings suggest new avenues for drug development targeting the sirtuin family, although further experimental validation and cross-species studies are needed to confirm translational relevance. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/657536v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1c397a3org.highwire.dtl.DTLVardef@188180org.highwire.dtl.DTLVardef@de1a59org.highwire.dtl.DTLVardef@193e740_HPS_FORMAT_FIGEXP M_FIG C_FIG

Source connections

Published article ↗

Explore related subjects

bioinformatics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Yang, J., Zhang, L., Yang, B., Ding, T., Zhao, Y., Yang, Y., Tang, X., Wu, Y., Wang, Q., Zhang, Z., Shi, C., Han, R., Zhang, X., Liu, J.. 2025-06-06. Global profiling of the proteome and acetylome in mice with abdominal aortic aneurysms. https://doi.org/10.1101/2025.06.02.657536

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

AF3 Inspector: In-Browser 3D Model Visualization and Confidence Analytics for AlphaFold 3

AlphaFold 3 (AF3) has broadened the computational structural biology landscape by predicting all-atom complexes across proteins, nucleic acids, small-molecule ligands, and ions, including chemical modifications. For non-experts, Google provides a fully web-based service to utilize AlphaFold 3. Unfortunately, despite a flexible and rich interface for inputs, the server's outputs are incomplete and complicated for many users, as witnessed hands-on. Not all confidence metrics are displayed, and those that are shown do not present much interactivity; besides, only model number 1 is shown among the 5 produced by the software, and upon download the user finds the models are provided only in CIF format, which is not yet well-known especially among highly practical users. Here, we present the AlphaFold 3 Multi-Model Inspector (AF3 Inspector, https://pdbms.altervista.org/af3viewer/afviewer8.html), an open, client-side, zero-install web application designed to dissect, align, and interactively explore the complete ensemble of structural models produced by AlphaFold 3. Part of the PDB Manipulation Suite (https://pdbms.altervista.org/), the AF3 Inspector operates entirely within web browsers, meaning it is available out of the box in all devices and operating systems. AF3 Inspector delivers 3D visualization in various styles and colors for all models, overlay with backbone alignment if requested, interactive plots for pLDDT profiles, pAE matrices and contact maps, chain-pair interaction heatmaps, automated detection of ligands, ions and post-translational modifications, and rapid mmCIF-to-PDB conversion allowing users to download the more familiar files. The platform addresses critical practical considerations highlighted in recent community benchmarks, such as CASP16, and extends the lightweight, client-side biophysical toolkit paradigm established by the PDB Manipulation Suite (PDBMS).

bioinformatics↗

bioRxiv2026

PanVasc Research for AI assisted evidence analysis in panvascular intervention

Panvascular intervention research requires evidence workflows that preserve source identity, outcome definitions and observation windows. We developed PanVasc Research, an executable research framework, and evaluated a fixed local Qwen3-4B model using two complementary tasks. Fifty ClinicalTrials.gov records from five vascular query strata generated 200 source-fidelity tests with intact evidence or controlled removal of the requested source, primary outcome or timeframe, plus 50 clean controls. A separate 100-statement sample from the official NLI4CT test set assessed clinical-trial entailment and evidence selection against existing expert labels. Generic and checklist prompts used identical evidence and maximum generation budgets; each output was also evaluated with an input-only deterministic contract. Registry exact accuracy was 51/200 (25.5%) with the generic prompt and 77/200 (38.5%) with the checklist; intact-case agreement was 50/50 and 48/50. The rule baseline recovered 200/200 tuples. NLI label accuracy was 48/100 (48.0%) and 50/100 (50.0%), respectively. The source contract retained 35 and 31 incorrect NLI labels in the two arms. Registry references establish fidelity to a registration snapshot, while NLI4CT concerns breast-cancer trials and does not validate vascular expertise. The framework also retains provenance-recorded literature retrieval, structured research planning and local numerical analysis. These experiments support a bounded assessment of source handling and semantic failure, rather than a new foundation model or autonomous scientific discovery. A proposed endpoint representation identifies the additional domain annotation and independent validation required for a panvascular research model.

bioinformatics↗

bioRxiv2026

BiomiX 3.0: A user-friendly platform for democratized multi-omics integration with graph-based learning.

Background Multi-omics integration has emerged as a powerful strategy to decode the molecular complexity of biological systems. However, the diversity of available methods, each designed with distinct assumptions, objectives, and computational requirements, makes method selection, usage and interpretation challenging for nonexpert users. Here we present BiomiX 3.0, an updated version of the BiomiX platform that extends its integration capabilities with four additional methods: Similarity Network Fusion (SNF), NEighborhood-based Multi-Omics clustering (NEMO), Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies (DIABLO), and PRAMIGO (Phenotyping netwoRk Application for Multi-omics InteGratiOn), a novel supervised heterogeneous graph transformer (HGT) introduced in this work. Results We benchmarked all five methods, MOFA, DIABLO, SNF, NEMO, and PRAMIGO, on two independent multiomics datasets derived from a Chronic Lymphocytic Leukemia (CLL) cohort comparing IGHV-mutated and unmutated patients, and a pulmonary tuberculosis (PTB) cohort versus healthy controls. Supervised methods (DIABLO, PRAMIGO) consistently achieved higher condition-specific discrimination as measured by the Adjusted Rand Index (ARI) and the Adjusted Mutual Information (AMI). In contrast, unsupervised methods (SNF, NEMO) revealed alternative patient stratifications driven by independent sources of biological variance while MOFA performed in a semi-supervised way occupies an intermediate position, capturing latent factors that explain both disease-associated and orthogonal sources of variance. Systematic gene-centric analysis of the top-ranked features prioritized by each method was supported by manual biological annotation of shared and method-specific signals. Across cohorts, we annotated 154 shared features (116 genes, 38 metabolites) and 60 method-unique features per cohort, demonstrating that no single integration strategy captures the full landscape of biologically relevant signals. In the CLL cohort, shared features spanned B-cell receptor biology, innate immune signaling, RAS/MAPK activation, and epigenetic regulation, while methodunique features revealed supervised-method-specific insights into vesicle trafficking (DIABLO), immune checkpoints (MOFA), and ncRNA regulation (PRAMIGO). In the PTB cohort, a convergent interferon/innate immune signature dominated shared features across all methods. Still, method-unique analysis uncovered DIABLO-specific acylcarnitine metabolic reprogramming, MOFA-specific restoration of lysosomal trafficking, and PRAMIGO-specific {gamma}{delta} T-cell and immunoglobulin repertoire diversity. Across both cohorts, SNF and NEMO proved useful for detecting biological and technical sources of variation that were orthogonal to the primary condition of interest. Ultimately, PRAMIGO uniquely enables the construction of heterogeneous graphs modeling cross-modal molecular interactions, uncovering epigenetic co-regulation programs in CLL and multi-omics inflammatory modules in PTB that are difficult to identify using conventional integration approaches. Conclusions BiomiX 3.0 provides a graphical user interface (GUI) multi-method integration environment that democratizes access to state-of-the-art multi-omics analysis. By combining both unsupervised and supervised integration strategies within a unified platform and introducing graph-based learning through PRAMIGO, BiomiX 3.0 enables researchers across disciplines with complementary tools to interrogate the biological sources of variation in their data, without requiring bioinformatics expertise.

bioinformatics↗