Biology subjects

Innocenti, G.

Publications and source records attributed to Innocenti, G..

6 recordsLinked to original sources

bioRxiv2026

Systemic antibody repertoires target specific microbial antigens in patients with colorectal cancer

Colorectal cancer (CRC) represents the third leading cause of cancer related deaths worldwide and is influenced by multiple risk factors. Both exposure to microbiota as well as adaptive immune responses have been implicated in CRC development and suggested as candidate biomarkers. However, the extent to which CRC and adenomas associate with systemic immune signatures against microbes remains unclear. Here, we apply Phage-display ImmunoPrecipitation Sequencing (PhIP-Seq) on 321 individuals of an Austrian CORSA cohort (Colorectal Cancer Study of Austria) including controls, adenomas, and CRC patients. Although antibody repertoires showed global similarity across the different disease status and limited predictive performance, prevalence-based analyses revealed specific signals, such as Helicobacter pylori CagY as candidate marker of CRC and viral antigens as candidate for non-cancer stages. Taken together, this large-scale analysis of antibody reactivity in CRC highlights the potential of serological markers to reflect disease-associated immune signatures.

immunology↗

bioRxiv2026

Slow relaxation oscillations in multi-scale adaptive next generation neural masses

We have studied the emergence of slow relaxation oscillations in next generation neural mass models with spike frequency adaptation. Relaxation oscillations connect low firing state (Down state) to high firing state (Up state) via the slow adaptation. In the examined cases, the orbit relaxes towards the Up State via a sequence of collective damped oscillations (peaks of activity), thus revealing population bursting dynamics. The slower is the adaptation time scale the higher is the complexity (number of peaks) displayed by the relaxation oscillations. In particular, a chaos-induced spike-adding mechanism regulates the increase in the number of peaks. In analogy to what found in the Hidmarsh-Rose neuron model, two different types of chaotic behaviors have been identified: Population Spiking and Population Bursting Chaos. The increase of the adaptation strength leads to shorter (longer) Up (Down) state durations somehow mimicking the effect of charbachol in in vitro experiments, where spontaneous slow waves are observed. Indeed, the scenario depicted in [1], where an increase of the concentration of carbachol induces a transition from anesthesia-like to sleep-like dynamics is consistent with our results based on the variation of the adaptation strength. HighlightsO_LISpike Frequency Adaptation (SFA) promotes the emergence of Slow Relaxation Oscillations C_LIO_LISpike-adding mechanisms, controlled by SFA, lead to Relaxation Oscillations of increasing complexity C_LIO_LITwo types of chaotic behaviours: Population Spiking and Population Bursting Chaos C_LIO_LISFA regulates Up and Down States durations and their correlation C_LI

neuroscience↗

bioRxiv2025

Phage-display immunoprecipitation sequencing reveals distinct antibody repertoire patterns across a rural-urban gradient

Environmental microbial exposures are hypothesized to drive immune profile differences across rural-urban gradients, yet direct evidence linking exposures to immune phenotypes remains limited. Here, we employed phage-displayed immunoprecipitation sequencing (PhIP-seq) to profile antibody repertoires against 357,192 epitopes from >700 organisms in 62 age-matched healthy adults from rural Senegal (n=29), urban Senegal (n=20), and urban Netherlands (n=13). PhIP-Seq analysis identified two major patterns of antibody repertoire variation: geographically restricted signatures distinguishing Senegal from the Netherlands, and a trajectory associated with rural-urban gradients spanning from rural Senegal to urban Netherlands. Integration of PhIP-seq data with high-dimensional immunological profiling revealed immune signatures correlated with the rural-urban antibody repertoire trajectory. Our findings demonstrate that antibody repertoire profiling captures distinct microbial exposure histories across both geographic regions and rural-urban gradients and correlates with variation in immune signatures. This work establishes PhIP-seq as a powerful tool for linking environmental exposure histories to population-level immune landscapes and provides insights into immune adaptation across diverse environments.

immunology↗

bioRxiv2023

Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections

The emergence and rapid spread of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and for guiding public health interventions. In particular, the Omicron variant underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them as soon as they emerge. In this study we applied a method based on mutual information (MI) between positions in a multiple sequence alignment (MSA), which is capable of scaling up to millions of samples. We showed how it could reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We tested this possibility by modifying the method to account for sample collection date and applied it retrospectively to MSAs for each month between March 2020 and March 2023. We could detect a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as 6 samples with a double mutation were present in the dataset, thus demonstrating the methods sensitivity. Lastly we provide examples of predicted interactions between genes, which are harder to test experimentally and therefore more likely to be overlooked. This method could become part of continuous surveillance systems tracking present and future pathogen outbreaks.

microbiology↗

bioRxiv2022

Assessing the influence of the Mediterranean diet on dental calculus microbiome composition: a pilot study

Human oral microbiome harbours hundreds of bacterial species, which, during evolution, assembled in different niches, such as the microbiome of saliva, tongue, hard palate, gingiva and dental plaque. Among these, saliva has been the most studied ecological niche of the oral microbiome. In this frame, scientific research has demonstrated that several factors concur to determine the saliva microbial composition, including diet, systemic diseases and drugs. However, the influence of such variables on other oral niches, such as the dental calculus, a calcified derivative of dental plaque, is still unexplored. During the last decade, dental calculus has become the primary target for evolutionary microbiome studies because of its ability to keep both bacterial DNA and dietary molecules (i.e., proteins and starch). As a consequence, dental calculus is now considered a powerful tool for obtaining information about oral microbiome composition, diet and individual health status in past populations, making it also appealing for clinical research. Here, we provide the first clinical study, to our knowledge, assessing the inter-variability of dental calculus microbiome in 40 patients. Samples were collected during routine dental inspection and analysed through 16S amplicon sequencing. In addition, we investigated the relationship between oral microbiome and host. Specifically, we tested the influence of Mediterranean diet style on the composition and functional pathways of oral bacteria, with the aim to test the dental calculus as a clinical bio-marker for diet impact and health status.

microbiology↗

bioRxiv2020

Tractography dissection variability: what happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

neuroscience↗