Biology subjects

Catalano, C.

Publications and source records attributed to Catalano, C..

9 recordsLinked to original sources

bioRxiv2026

FiberBrowser: a unified framework for single-molecule genomics

Single-molecule footprinting methods are rapidly transforming chromatin biology. They resolve nucleosome positioning, regulatory-factor occupancy, and accessibility on individual DNA fibers, revealing combinatorial heterogeneity that bulk measurements average away. Emerging footprinting methods leverage diverse enzyme systems and sequencing platforms, necessitating tools that can accommodate these systems. We present FiberBrowser, a unified platform that converts these diverse datasets into a common per-molecule representation of nucleosomes, accessible DNA, and subnucleosomal footprints for interactive and scripted analyses. Its inference engine, FiberHMM, weighs each observation against the assay's informative sites and sequence-specific modification probabilities, separating missing information from protection in four assays. FiberBrowser clusters, sorts and compares these calls across thousands of molecules in seconds, linking chromatin architecture to haplotype, CpG methylation and non-reference structural variants on the same molecules. Because the representation is independent of chemistry, models also transfer between assays. A classifier trained on Fiber-seq footprints identifies 12 scDAF-seq cells as lymphoblastoid without retraining, whereas models trained on raw modification patterns fail to transfer. FiberBrowser thus provides a unified, expandable analytical framework for single-molecule chromatin footprinting.

genomics↗

bioRxiv2026

Evolution of compound eye cell types shapes visual behaviors across Heliconius butterflies

The evolution of visual systems is tightly linked to the diversification of visually guided behaviors. Using Heliconius butterflies, renowned for their rapid diversification of wing color patterns and corresponding visual mate preferences, we investigate the evolution of compound eye cell types across a complete speciation continuum. By integrating population genomics, chromatin conformation capture, and single-nucleus multi-omics, we uncover multi-modal mechanisms driving visual system evolution. Within a population polymorphic for mate preference, we identify senseless-2 as a glia-expressing candidate visual preference gene. Across species, we reveal that photoreceptors, particularly the color-sensing R7s, are the fastest-evolving cell types. Furthermore, we molecularly characterize novel R2/5 and R7 photoreceptor subtypes, showing that cellular subfunctionalization arises through the co-option of existing gene regulatory networks. Together, this comparative single-cell analysis of compound eyes bridges microevolutionary transcriptomic divergence with macroevolutionary cellular innovations.

evolutionary biology↗

bioRxiv2026

Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis

Protein evolution is constrained by multidimensional biophysical factors, in which mutations that enhance one property often compromise another. Antibodies represent an extreme case: they evolve rapidly to bind diverse antigens, yet mutations that improve affinity can disrupt folding, reduce cell-surface trafficking, or promote self-reactivity, and are typically selected against during affinity maturation. Though biophysical characterization of individual antibodies suggests that such trade-offs are pervasive, their impact on antibody evolutionary trajectories remains unclear, in part because existing high-throughput biophysical methods rely on heterologous systems that are often poorly suited for human proteins. Here, we develop a high-throughput platform to quantify multiple biophysical parameters of large libraries of full-length proteins that are natively synthesized, processed, and displayed on human cells. We apply this approach to a human antibody lineage that matures to recognize divergent SARS-CoV-2 variants by measuring the surface expression, antigen affinity, and self-reactivity for all 213 possible evolutionary intermediates between the unmutated and mature sequences. These measurements reveal that mutations differentially affect these biophysical properties - in some cases, improving one property at the expense of another. We leverage these data to compute the likelihood of all possible evolutionary paths, finding that very few paths can navigate these multidimensional requirements. The few accessible paths acquire mutations in a specific order that either circumvent trade-offs between biophysical properties or offset deleterious effects on one property with beneficial effects on another. By determining the structures of the ancestral and evolved antibodies, we find that these coordinated mutational effects arise from a conformational rearrangement that alleviates steric clashes and reshapes the biophysical landscape, enabling otherwise inaccessible mutational paths. Together, this work defines the multidimensional biophysical constraints and structural mechanisms that govern antibody evolution and establishes a general framework for mapping and predicting the biophysical effects of mutations in human proteins.

evolutionary biology↗

bioRxiv2025

Personalized computational hemodynamic analysis in transcatheter aortic valve: investigation of long-term degeneration

Introduced as an alternative to open-heart surgery for elderly patients, Transcatheter Aortic Valve Implantation (TAVI) has recently been extended to younger patients due to comparable performance with the gold-standard. However, the long-term durability of the bio-prosthetic TAVI valves is limited by Structural Valve Deterioration (SVD), an inevitable degenerative process whose pathogenesis is still unclear. In this study, we aim to computationally investigate a possible relation between aortic hemodynamics and SVD development. To this aim, we collect data from twelve patients with and without SVD at long-term follow-up exams. Starting from pre-operative clinical images, we build early post-operative virtual scenarios and we perform Computational Fluid Dynamics simulations by prescribing a personalized flow rate based on Echo Doppler data. In order to identify a premature onset of SVD, we propose three computational hemodynamic indices: Wall Damage Index (WDI), Leaflet Delamination Index (LDI), and Leaflet Permeability Index (LPI). Additionally, to each index we associate a score and, using the Wilcoxon rank-sum test, we find that each score individually shows a statistically greater median value in the SVD sub-population (WDI: p = 0.008, LDI: p = 0.001, LPI: p = 0.020). Finally, we define a synthetic scoring system that clearly separates between SVD and non-SVD patients. Our results suggest that aortic hemodynamics may drive a premature onset of SVD, and the synthetic score could potentially assist clinicians in a patient-specific planning of follow-up exams to closely monitor those patients at high SVD risk.

bioengineering↗

bioRxiv2025

Community Challenge towards Consensus on Characterization of Biological Tissue: C4Bios First Findings

This study investigates methodological variability across various expert laboratories worldwide, with regards to characterizing the mechanical properties of biological tissues. Two testing rounds were conducted on the specific use case of uniaxial tensile testing of porcine aorta. In the first round, 24 labs were invited to apply their established methods to assess inter-laboratory variability. This revealed significant methodological diversity and associated variability in the stress-stretch results, underscoring the necessity for a standardized approach. In the second round, a consensus protocol was collaboratively developed and adopted by 19 labs in an attempt to minimize variability. This involved standardized sample preparation and uniformity in testing protocol, including the use of a common cutting and thickness measurement tool. Despite protocol harmonization, significant variability persisted across labs, which could not be solely attributed to inherent biological differences in tissue samples. These results illustrate the challenges in unifying testing methods across different research settings, underlining the necessity for further refinement of testing practices. Enhancing consistency in biomechanical experiments is pivotal when comparing results across studies, as well as when using the resulting material properties for in silico simulations in medical research.

bioengineering↗

bioRxiv2024

Snapshots of Pseudomonas aeruginosa SOS response activation complex reveal structural prerequisites for LexA engagement and cleavage

Antimicrobial resistance represents a major threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response to DNA damage plays a pivotal role in bacterial evolution, driving the development of resistance mechanisms and influencing the adaptability of bacterial populations to challenging environments, particularly in the context of antibiotic exposure. Recombinase A (RecA) and the transcriptional repressor LexA are the key players that orchestrate this process, determining either the silencing or the active transcription of the genes under their control. By integrating state-of-the-art structural approaches with binding and functional assays in vitro, we elucidated the molecular events governing the SOS response activation in P. aeruginosa, focusing on the RecA-LexA interaction. Our findings identify the conserved determinants and strength of the interactions that let RecA trigger the autocleavage and inactivation of the LexA repressor. These results provide the groundwork for designing novel antimicrobial strategies and for exploring the potential translation of Escherichia coli-derived approaches, to address the health-threatening implications of bacterial infections. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/585941v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@2fe1e4org.highwire.dtl.DTLVardef@19741e1org.highwire.dtl.DTLVardef@1664ddborg.highwire.dtl.DTLVardef@18195cb_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

The CryoEM structure of human serum albumin in complex with ligands

Human serum albumin (HSA) is the most prevalent plasma protein in the human body, accounting for 60% of the total plasma protein. HSA plays a major pharmacokinetic function, serving as a facilitator in the distribution of endobiotics and xenobiotics within the organism. In this paper we report the cryoEM structures of HSA in the apo form and in complex with two ligands (salicylic acid and teniposide) at a resolution of 3.5, 3.7 and 3.4 [A], respectively. We expand upon previously published work and further demonstrate that sub-4 [A] maps of [~]60 kDa proteins can be routinely obtained using a 200 kV microscope, employing standard workflows. Most importantly, these maps allowed for the identification of small molecule ligands, emphasizing the practical applicability of this methodology and providing a starting point for subsequent computational modeling and in silico optimization.

biochemistry↗

bioRxiv2022

Membrane-active Polymers: NCMNP13-x, NCMNP21-x and NCMNP21b-x for Membrane Protein Structural Biology

Membrane proteins are a ubiquitous group of bio-macromolecules responsible for many crucial biological processes and serve as drug targets for a wide range of modern drugs. Detergent-free technologies such as styrene-maleic acid lipid particles (SMALP), diisobutylene-maleic acid lipid particles (DIBMALP), and native cell membrane nanoparticles (NCMN) systems have recently emerged as revolutionary alternatives to the traditional detergent-based approaches for membrane protein research. NCMN systems aim to create a membrane-active polymer library suitable for high-resolution structure determination. Herein, we report our design, synthesis, characterization and comparative application analyses of three novel classes of NCMN polymers, NCMNP13-x, NCMNP21-x and NCMNP21b-x. Although each NCMN polymer can solubilize various model membrane proteins and conserve native lipids into NCMN particles, only the NCMNP21b-x series reveals lipid-protein particles with good buffer compatibility and high homogeneity suitable for single-particle cryo-EM analysis. Consequently, the NCMNP21b-x polymers that bring out high-quality NCMN particles are particularly attractive for membrane protein structural biology. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/475744v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@dbc1f3org.highwire.dtl.DTLVardef@19a5ff0org.highwire.dtl.DTLVardef@10beceorg.highwire.dtl.DTLVardef@15ec66a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDemonstrate straightforward strategies for tailoring styrene-maleic co-polymer (SMA) that revealed novel buffer compatible polymers, NCMNP13-50, NCMNP21-20 and NCMNP21b-x. C_LIO_LIElucidate how modification factors alter the membrane-active properties of these polymers, i.e., membrane protein extraction efficiency, morphology, etc. C_LIO_LIProvide valuable insights into the rational design of membrane-active polymers for membrane protein structural biology. C_LIO_LINCMNP21b-x polymers are highly compatible with high-resolution structure determination using an emerging technique, cryo-EM. C_LI

biochemistry↗

bioRxiv2021

The haplotype-resolved reference genome of lemon (Citrus limon L. Burm f.)

Lemon (Citrus limon (L.) Burm. f.) is an evergreen tree belonging to the genus Citrus. The fruits are particularly prized for their organoleptic and nutraceutical properties of the juice. Herein we report, for the first time, the release of a high-quality reference genome of the two haplotypes of lemon. The sequencing has been carried out coupling Illumina short reads and Oxford Nanopore data leading to the definition of a primary and an alternative assembly characterized by a genome size of 312.8 Mb and 324.74 Mb respectively. The analysis of the long terminal repeat (LTR) allowed the identification of 1921 regions on the primary and 1911 on the alternative assembly distributed across the nine chromosomes. Furthermore, an in-silico analysis of the microRNA genes was carried out using 246 mature miRNA and the respective pre-miRNA hairpin sequences of C. sinensis. Such analysis highlighted a high conservation between the two species with 233 mature miRNAs and 51 pre-miRNA stem-loops aligning with perfect match on the lemon genome. In parallel, total RNA was extracted from fruit, flower, leaf and root enabling the detection of 38,205 and 37,753 predicted transcripts on primary and alternative assemblies respectively. Among those, the highest and lowest number of tissue-specific transcripts were detected in flower (2.73% and 2.71% in primary and alternative assemblies respectively) and leaf (0.7% and 0.68%) while gene ontology analysis enables a more precise characterization of the expressed genes based on their function. The availability of a reference genome is an important prerequisite both for the set-up of high-throughput genotyping analysis and for functional genomic approaches toward the characterization of the genetic determinism of traits of agronomic interest.

genomics↗