FibrilNet maps conserved and tissue-specific molecular environments across systemic amyloidoses
- 1University of Catanzaro
Abstract
Systemic amyloidoses are initiated by distinct amyloidogenic precursor proteins but frequently contain recurrent extracellular, complement, lipid-transport and matrix-remodelling components. Whether these recurrent proteins form a conserved systems-level environment across amyloid diseases, and how strongly that environment depends on precursor and tissue context, remains unresolved. We developed FibrilNet, a network framework that integrates experimentally defined amyloid proteomes with a human protein protein interaction graph and Gene Ontology derived semantic information. FibrilNet compares topology-only random walk with restart (RWR) with ontology aware semantic RWR in frozen leave-one-out module reconstruction and precursor-seeded prioritization tasks. The human graph contains 17,997 proteins and 925,977 physical interactions, with a 9-dimensional semantic representation of interaction context. In expanded cardiac transthyretin amyloidosis (ATTR), semantic-RWR increased mean reciprocal rank (MRR) from 0.00167 to 0.05015 and Recall@100 from 0.0199 to 0.3377, improving 132 of 151 held-out targets. Significant semantic gains were also observed in renal serum amyloid A amyloidosis (AA) and leukocyte chemotactic factor 2 amyloidosis (ALECT2). Across compact ATTR, light-chain amyloidosis (AL), AA and ALECT2 modules, APCS, VTN and TIMP3 formed a direct four-disease recurrent core, while APOE occurred in three of four modules. A tissue-aware ATTR analysis showed limited overlap between cardiac and neurologic modules (19 shared proteins; Jaccard 0.0569). In the hTTR-A97S peripheral-nerve model, semantic-RWR significantly improved reconstruction of the 202-protein mapped neurologic module, with the strongest evidence concentrated in the downregulated proteomic program. TTR-seeded propagation improved with semantic information but remained weak in absolute terms, separating precursor identity from the distributed downstream molecular environment. These results support a multilayer model in which a restricted conserved amyloid environment coexists with precursor-, tissue- and disease-specific organization
Related
- Cross-species molecular mapping of the photoreceptor sensory cilium and periciliary structures identifies conserved and species-specific architectural features
- An integrated multi-omic atlas of the choroid plexus highlights conserved molecular programs of epithelial function
- Conserved and species-specific guard cell transcriptional responses and drought physiology in Arabidopsis and tomato
- Cell-type-specific coupling of single-unit spikes to cortical ripples conserved across macaque and human V1
- A transcriptome map reveals conserved and lineage-specific sRNAs that regulate motility and metabolism across Vibrio
BibTeX
@misc{guzzi2026fibrilnet,
title = {{FibrilNet maps conserved and tissue-specific molecular environments across systemic amyloidoses}},
author = {P. H. Guzzi and L. H. Ugo and V. Carbonari and P. Lio' and P. Veltri},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.747993},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.747993v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - FibrilNet maps conserved and tissue-specific molecular environments across systemic amyloidoses
AU - P. H. Guzzi
AU - L. H. Ugo
AU - V. Carbonari
AU - P. Lio'
AU - P. Veltri
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.747993
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.747993v1
AB - Systemic amyloidoses are initiated by distinct amyloidogenic precursor proteins but frequently contain recurrent extracellular, complement, lipid-transport and matrix-remodelling components. Whether these recurrent proteins form a conserved systems-level environment across amyloid diseases, and how strongly that environment depends on precursor and tissue context, remains unresolved. We developed FibrilNet, a network framework that integrates experimentally defined amyloid proteomes with a human protein protein interaction graph and Gene Ontology derived semantic information. FibrilNet compares topology-only random walk with restart (RWR) with ontology aware semantic RWR in frozen leave-one-out module reconstruction and precursor-seeded prioritization tasks. The human graph contains 17,997 proteins and 925,977 physical interactions, with a 9-dimensional semantic representation of interaction context. In expanded cardiac transthyretin amyloidosis (ATTR), semantic-RWR increased mean reciprocal rank (MRR) from 0.00167 to 0.05015 and Recall@100 from 0.0199 to 0.3377, improving 132 of 151 held-out targets. Significant semantic gains were also observed in renal serum amyloid A amyloidosis (AA) and leukocyte chemotactic factor 2 amyloidosis (ALECT2). Across compact ATTR, light-chain amyloidosis (AL), AA and ALECT2 modules, APCS, VTN and TIMP3 formed a direct four-disease recurrent core, while APOE occurred in three of four modules. A tissue-aware ATTR analysis showed limited overlap between cardiac and neurologic modules (19 shared proteins; Jaccard 0.0569). In the hTTR-A97S peripheral-nerve model, semantic-RWR significantly improved reconstruction of the 202-protein mapped neurologic module, with the strongest evidence concentrated in the downregulated proteomic program. TTR-seeded propagation improved with semantic information but remained weak in absolute terms, separating precursor identity from the distributed downstream molecular environment. These results support a multilayer model in which a restricted conserved amyloid environment coexists with precursor-, tissue- and disease-specific organization
ER -