Biology subjects

Ferraro, E.

Publications and source records attributed to Ferraro, E..

5 recordsLinked to original sources

bioRxiv2026

The interferon-gamma response pathway is a targetable driver of FSHD muscular dystrophy progression

Facioscapulohumeral muscular dystrophy (FSHD) is a leading neuromuscular disorder caused by the aberrant expression of the transcription factor double homeobox 4 (DUX4) in skeletal muscle. While DUX4 is normally restricted to early embryonic development, its reactivation in FSHD triggers chronic inflammation and progressive muscle degeneration. However, the precise molecular links between DUX4 and persistent immune activation remain poorly understood. Here, we show that DUX4 induces a viral mimicry-like pathway that is fundamentally uncoupled from canonical type I interferon (IFN) activation. Instead, DUX4 establishes a non-canonical innate immune state dominated by IFN-gamma signaling, providing a mechanistic explanation for the non-resolving inflammation characteristic of the disease. We demonstrate that while IFN-gamma treatment alone is sufficient to recapitulate key DUX4 pathogenic effects, its inhibition rescues muscle inflammation and halts disease progression in FSHD models. These findings define a skewed viral mimicry process driven by a disease-specific transcription factor and identify IFN-gamma as a primary therapeutic target for tissue-informed immunomodulation in muscular dystrophy.

genetics↗

bioRxiv2025

Benchmarking generative AI tools for literature retrieval and summarization in genomic variant interpretation.

BackgroundGenerative AI is increasingly used to extract structured information across domains, but its reliability in academic and clinical research, where precision and accuracy are essential, remains largely unexplored. This study evaluates the ability of Large Language Models (LLMs)-based algorithms to generate accurate, literature-based summaries of human genomic variants, with a focus on real-world usability. ResultsWe benchmarked five open-access generative AI platforms--ChatGPT, MistralAI, VarChat, Perplexity, and ScholarAI--across 40 curated variants equally divided between somatic and germline settings. For each variant, summary reports were generated and blindly evaluated by domain experts using five defined metrics. VarChat emerged as the top-ranked tool, showing the highest summarization accuracy, citation relevance, and robustness against hallucinations. Gpt-4o consistently ranked second, showing particularly stable robustness in conditions where the literature was scarce. Perplexity and ScholarAI, despite being literature-focused, ranked lowest across most metrics. Tool performance was strongly influenced by the availability of peer-reviewed literature, confirming that current generative models remain sensitive to data scarcity. ConclusionsOur findings highlight the heterogeneity of current generative AI tools in genomic variant interpretation workflows. While some platforms already provide useful outputs, reliable integration into basic and clinical research requires expert validation and domain-related fine-tuning. This work provides for the first time a curated benchmark for assessing LLM-generated content in variant genomics and underscores the need for caution when using these tools to support variant interpretation.

bioinformatics↗

bioRxiv2021

Holosteans contextualize the role of the teleost genome duplication in promoting the rise of evolutionary novelties in the ray-finned fish innate immune system

Over 99% of ray-finned fishes (Actinopterygii) are teleosts, a clade that comprises half of all living vertebrates that have diversified across virtually all fresh and saltwater ecosystems. This ecological diversity raises the question of how the immunogenetic diversity required to persist under heterogeneous pathogen pressures evolved. The teleost genome duplication (TGD) has been hypothesized as the evolutionary event that provided the genomic substrate for rapid genomic evolution and innovation. However, studies of putative teleost-specific innate immune receptors have been largely limited to comparisons either among teleosts or between teleosts and distantly related vertebrate clades such as tetrapods. Here we describe and characterize the receptor diversity of two clustered innate immune gene families in the teleost sister lineage: Holostei (bowfin and gars). Using genomic and transcriptomic data, we provide a detailed investigation of the phylogenetic history and conserved synteny of gene clusters encoding diverse immunoglobulin domain-containing proteins (DICPs) and novel immune-type receptors (NITRs). These data demonstrate an ancient linkage of DICPs to the major histocompatibility complex (MHC) and reveal an evolutionary origin of NITR variable-joining (VJ) exons that predate the TGD by at least 50 million years. Further characterizing the receptor diversity of Holostean DICPs and NITRs illuminates a sequence diversity that rivals the diversity of these innate immune receptor families in many teleosts. Taken together, our findings provide important historical context for the evolution of these gene families that challenge prevailing expectations concerning the consequences of the TGD during actinopterygiian evolution.

immunology↗

bioRxiv2019

Movement and space-use responses of a large herbivore to experimental alteration of resource availability

The link between spatio-temporal resource patterns and movement behaviour is a key ecological process, however, limited experimental support has been produced at the home range scale. In this study, we analysed the spatial responses of a resident large herbivore (roe deer Capreolus capreolus) during an in situ manipulation of a concentrated food resource. Specifically, we experimentally altered feeding site accessibility to roe deer and recorded (for 25 animal-years) individual responses by GPS tracking. We found that, following the loss of their preferred resource, roe deer actively tracked resource dynamics leading to more exploratory movements, and larger, spatially-shifted home ranges. Then, we showed, for the first time experimentally, the importance of site fidelity in the maintenance of large mammal home ranges by demonstrating the return of individuals to their familiar, preferred resource despite the presence of alternate, equally-valuable food resources. This behaviour was modulated at the individual level, where roe deer characterised by a high preference for feeding sites exhibited more pronounced behavioural adjustments during the manipulation. Together, our results establish the connections between movement, space-use, individual preference, and the spatio-temporal pattern of resources in home ranging behaviour.

ecology↗

bioRxiv2019

Persistent anti-heart autoimmunity causes cardiomyocyte damage in chronic heart failure.

Although clinicians and researchers have long appreciated the detrimental effects of excessive acute inflammation after myocardial infarction (MI), less is known about the role of the adaptive immune system in MI complications including heart failure. Yet, abundant cardiac self-antigens released from necrotic cardiomyocytes in a highly inflammatory environment are likely to overwhelm peripheral mechanisms of immunological self-tolerance and adaptive auto-reactivity against the heart may cause ongoing tissue destruction and exacerbate progression to chronic heart failure (CHF). Here, we confirm that the adaptive immune system is indeed persistently active in CHF due to ischemic heart disease triggered by MI in rats. Heart draining mediastinal lymph nodes contain active secondary follicles with mature class-switched IgG2a positive cells, and mature anti-heart auto-antibodies binding to cardiac epitopes are still present in serum as late as 16 weeks after MI. When applied to healthy cardiomyocytes in vitro, humoral factors present in CHF serum promoted apoptosis, cytotoxicity and signs of hypertrophy. These findings directly implicate post-MI autoimmunity as an integral feature of CHF progression, constituting a roadblock to effective regeneration and a promising target for therapeutic intervention.

immunology↗