Marzia Rossato

• University Medical Center Utrecht

Key message The origin of common bean was investigated throughout chloroplast and nuclear WGS data considering recombination events. Our results support the Mesoamerican origin of common bean. Abstract The remarkable evolutionary history of the common bean (Phaseolus vulgaris L.) has led to the emergence of three wild main gene pools corresponding...

Background Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear. Methods This study investi...

MECP2 deficiency causes a broad spectrum of neuropsychiatric disorders that can affect both genders. Rett syndrome is the most common and is characterized by an apparently normal growth period followed by a regression phase in which patients lose most of their previously acquired skills. After this dramatic period, various symptoms progressively ap...

The common bean (Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905...

The domestication of crops, coupled with agroecosystem development, is associated with major environmental changes and provides an ideal model of phenotypic plasticity. Here, we examined 32 genotypes of three tetraploid wheat (Triticum turgidum L.) subspecies, wild emmer, emmer and durum wheat, which are representative of the key stages in the dome...

The structure of crop genetic diversity reflects spatial and ecological variations caused by population dynamics during adaptation to different agricultural environments. Landscape genomics can reveal patterns of neutral and adaptive variation related to environmental and spatial heterogeneity. We assembled a collection of 532 chickpea accessions a...

The green alga Haematococcus lacustris (formerly Haematococcus pluvialis) is a primary source of astaxanthin, a ketocarotenoid with high antioxidant activity and several industrial applications. Here, the Haematococcus lacustris highly repetitive genome was reconstructed by exploiting next-generation sequencing integrated with Hi-C scaffolding, obt...

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequenc...

Introduction Plasmacytoid dendritic cells (pDCs) infiltrate a large set of human cancers. Interferon alpha (IFN-α) produced by pDCs induces growth arrest and apoptosis in tumor cells and modulates innate and adaptive immune cells involved in anti-cancer immunity. Moreover, effector molecules exert tumor cell killing. However, the activation state a...

The common bean (Phaseolus vulgaris L.) is an important grain legume crop [1,2] whose life history offers an ideal evolutionary model to identify adaptive variants suitable for breeding programs [3]. Here we present the first common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. We found ~243 M...

The domestication of crops is associated with the genome-wide loss of nucleotide diversity caused by selection and genetic drift. Here we investigated 32 genotypes representing key stages in the domestication of tetraploid wheat, i.e. wild emmer, emmer and durum wheat. RNA-Seq analysis was combined with estimates of evolvability, heritability and Q...

The evolutionary history of the common bean (Phaseolus vulgaris) 1 revealed by chloroplast and nuclear genomes. Abstract 23 The remarkable evolutionary history of the common bean (Phaseolus vulgaris L.) has led to the 24 emergence of three wild main genepools corresponding to three different ecogeographic areas: 25 Mesoamerica, the Andes and northe...

High-throughput genotyping enables the large-scale analysis of genetic diversity in population genomics and genome-wide association studies that combine the genotypic and phenotypic characterization of large collections of accessions. Sequencing-based approaches for genotyping are progressively replacing traditional genotyping methods due to the lo...

Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiti...

Despite major advances in genome technology and analysis, >50% of patients with a neurodevelopmental disorder (NDD) remain undiagnosed after extensive evaluation. A point in case is our clinically heterogeneous cohort of NDD patients that remained undiagnosed after FRAXA testing, chromosomal microarray analysis and trio exome sequencing (ES). In th...

Xylella fastidiosa is a fastidious Gram-negative bacterium that is associated with several important plant diseases, and is regulated as a quarantine pest in many countries where strategies are implemented to prevent its introduction and spread. To enact efficient quarantine measures, effective and early detection of the pathogen are essential, esp...

High-throughput chromosome conformation capture (Hi-C) is widely used for scaffolding in de novo assembly because it produces highly contiguous genomes, but its indirect statistical approach can introduce connection errors. We employed optical mapping (Bionano Genomics) as an orthogonal scaffolding technology to assess the structural solidity of Hi...

Complete and accurate identification of genetic variants associated with specific phenotypes can be challenging when there is a high level of genomic divergence between individuals in a study and the corresponding reference genome. We have applied the Cas9-mediated enrichment coupled to nanopore sequencing to perform a targeted de novo assembly and...

High-throughput genotyping facilitates the large-scale analysis of genetic diversity in population genomics and genome-wide association studies that combine the genotypic and phenotypic characterization of large collections of wild and domesticated germplasm. Genotyping by sequencing is progressively replacing traditional genotyping methods due to...

Despite major technical and genetic advances, more than half of the neurodevelopmental disorders (NDDs) cases remain undiagnosed. We explored the frequency of non-random XCI in the mothers of male patients and in affected females from a clinically heterogeneous cohort of unsolved NDD cases, negative at FRAXA, chromosomal microarray analysis and Tri...

Myotonic dystrophy type 2 (DM2) is caused by CCTG repeat expansions in the CNBP gene, comprising 75 to >11,000 units and featuring extensive mosaicism, making it challenging to sequence fully-expanded alleles. To overcome these limitations, we used PCR-free Cas9-mediated nanopore sequencing to characterize CNBP repeat expansions at the single-nucle...

Diagnostic tests based on reverse transcription–quantitative polymerase chain reaction (RT–qPCR) are the gold standard approach to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from clinical specimens. However, unless specifically optimized, this method is usually unable to recognize the specific viral strain respons...

The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, we try to elucidate whether t...

Myotonic dystrophy type 2 (DM2) is caused by CCTG repeat expansions in the CNBP gene, comprising 75 to >11,000 units and featuring extensive mosaicism, making it challenging to sequence fully-expanded alleles. To overcome these limitations, we used PCR-free Cas9-mediated nanopore sequencing to characterize CNBP repeat expansions at the single-nucle...

Background ‘Nebbiolo’ is a grapevine cultivar typical of north-western Italy, appreciated for producing high-quality red wines. Grapevine cultivars are characterized by possessing highly heterozygous genomes, including a great incidence of genomic rearrangements larger than 50 bp, so called structural variations (SVs). Even though abundant, SVs are...

Objectives To identify key disease pathways driving conventional dendritic cell (cDC) alterations in Systemic Sclerosis (SSc). Methods Transcriptomic profiling was performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 SSc patients with all major disease subtypes. Differential expression analysis comparing the diff...

Mummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic herita...

Traditional methods for the analysis of repeat expansions, which underlie genetic disorders, such as fragile X syndrome (FXS), lack single-nucleotide resolution in repeat analysis and the ability to characterize causative variants outside the repeat array. These drawbacks can be overcome by long-read and short-read sequencing, respectively. However...

Objective Systemic sclerosis (SSc) is a complex disease characterized by vascular abnormalities and inflammation culminating in hypoxia and excessive fibrosis. Previously, we identified CXCL4 as a novel predictive biomarker in SSc. Although CXCL4 is well-studied, the mechanisms driving its production are unclear. The aim of this study was to elucid...

Mummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic herita...

Ageing is among the main risk factors for human disease onset and the identification of the hallmarks of senescence remains a challenge for the development of appropriate therapeutic target in the elderly. Here, we compare senescence-related changes in two cell populations of mesenchymal stromal cells by analysing their miRNA profiling: Human Denta...

Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of the IFN respons...

Sequencing the SARS-CoV-2 genome from clinical samples can be challenging, especially in specimens with low viral titer. Here we report Accurate SARS-CoV-2 genome Reconstruction (ACoRE), an amplicon-based viral genome sequencing workflow for the complete and accurate reconstruction of SARS-CoV-2 sequences from clinical samples, including suboptimal...

Compelling evidence shows the involvement of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc) pathogenesis. This study investigated whether microRNAs (miRNAs) are involved in the dysregulation of pDCs in SSc patients already at early stages. RNA from circulating pDCs was isolated from two independent cohorts of SSc patients with diff...

We report Accurate SARS-CoV-2 genome Reconstruction (ACoRE), an amplicon-based viral genome sequencing workflow for the complete and accurate reconstruction of SARS-CoV-2 sequences from clinical samples, including suboptimal ones that would usually be excluded even if unique and irreplaceable. We demonstrated the utility of the approach by achievin...

Background: Leiomyoma are the most common indication for hysterectomy in the world and have a strong economic impact on health care systems; many different mechanisms have been considered for their aetiology, such as inflammation, dysregulated progenitor cells or different regulation of miRNAs. After performing a whole genome miRNA profiling in pro...

Background: Leiomyoma are the most common indication for hysterectomy in the world and have a strong economic impact on health care systems; many different mechanisms have been considered for their aetiology, such as inflammation, dysregulated progenitor cells or different regulation of miRNAs. After performing a whole genome miRNA profiling in pro...

To elucidate the physiology underlying the development of superficial scald in pears, susceptible "Blanquilla" fruit was treated with different compounds that either promoted (ethylene) or repressed (1-methylcyclopropene and lovastatin) the incidence of this disorder after 4 months of cold storage. Our data show that scald was negligible for the fr...

Despite sharing many of the traits that have allowed the genus Bacillus to gain recognition for its agricultural relevance, the genus Lysinibacillus is not as well-known and studied. The present study employs in vitro, in vivo, in planta, and in silico approaches to characterize Lysinibacillus fusiformis strain S4C11, isolated from the roots of an...

The reconstruction of individual haplotypes can facilitate the interpretation of disease risks; however, high costs and technical challenges still hinder their assessment in clinical settings. Second-generation sequencing is the gold standard for variant discovery but, due to the production of short reads covering small genomic regions, allows only...

Highlight: Linkage mapping, the histological and the expression pattern analyses in pods identified PvMYB26 as the best candidate gene for pod indehiscence, that is mediated by a non-functional abscission layer in the pod. ABSTRACT In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes se...

In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes seed dispersal. In Phaseolus vulgaris (L)., the major locus qPD5.1-Pv for pod indehiscence was identified recently. We developed a BC4/F4 introgression line population and narrowed the major locus down to a 22.5-kb region. Here, gene...

Structural Variants (SVs) are a widely unexplored source of genetic variation, both due to methodological limitations and because they are generally associated to deleterious effects. However, with the advent of long-range genomic platforms, it has become easier to directly detect SVs. In the same direction, clonally propagated crops provide a uniq...

Background: Patients with glioblastoma (GBM) have a dramatically poor prognosis. The recent REGOMA trial suggested an overall survival benefit of regorafenib in recurrent GBM patients. Considering the extreme genetic heterogeneity of GBMs, we aimed to identify molecular biomarkers predictive of differential response to the drug. Methods: Total R...

Anthropogenic environmental change is leading to changes in distribution for many organisms. While this is frequently discussed for prominent organisms of high conservation value, the same is true for the many cryptic species that rarely figure in debates on the human impact. One such cryptic taxon is the European Ptomaphagus sericatus (Chaudoir, 1...

Systemic sclerosis (SSc) is a rare chronic disease of unknown pathogenesis characterized by fibrosis of the skin and internal organs, vascular alteration, and dysregulation of the immune system. In order to better understand the immune system and its perturbations leading to diseases, the study of the mechanisms regulating cellular metabolism has g...

In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes seed dispersal. In Phaseolus vulgaris , the major locus qPD5.1-Pv for pod indehiscence was identified recently. We developed a BC4/F4 introgression line population and narrowed the major locus down to a 22.5-kb region. Here, gene expr...

Objective To analyze how monocyte and macrophage exposure to CXCL4 induces inflammatory and fibrotic processes observed in Systemic sclerosis (SSc) patients. Methods In six independent experiments, monocytes of healthy controls (HC) and SSc patients were stimulated with CXCL4, TLR-ligands, IFNɑ or TGFβ and the secretion of cytokines in the superna...

Several research studies were focused to understand how grapevine cultivars respond to environment; nevertheless, the biological mechanisms tuning this phenomenon need to be further deepened. Particularly, the molecular processes underlying the interplay between clones of the same cultivar and environment were poorly investigated. To address this i...

Four new species, Grouvellinus nigerquadratus sp. nov., G. cruxniger sp. nov., G. luciaensis sp. nov., and G. borneensis sp. nov., are described from Borneo and illustrated in detail. Two additional species of the genus which remain undescribed are briefly diagnosed. The material was collected during Taxon Expeditions’ field course which involved c...

Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune‐cells in 169 patients with these SADs and 44 healty controls (HC) using mass‐cytometry and assessed the diagnost...

Primary Sjögren's syndrome (pSS) is a systemic auto-immune disease typified by dryness of the mouth and eyes. A majority of patients with pSS have a type-I interferon (IFN)-signature, which is defined as the increased expression of IFN-induced genes in circulating immune cells and is associated with increased disease activity. As plasmacytoid dendr...

Tlarge granular lymphocyte leukemia (T-LGLL) is characterized by the expansion of several large granular lymphocyte clones, among which a subset of large granular lymphocytes showing constitutively activated STAT3, a specific CD8+/CD4- phenotype and the presence of neutropenia has been identified. Although STAT3 is an inducer of transcription of a...

Chlorella vulgaris is a fast‐growing fresh‐water microalga cultivated at the industrial scale for applications ranging from food to biofuel production. To advance our understanding of its biology and to establish genetics tools for biotechnological manipulation, we sequenced the nuclear and organelle genomes of Chlorella vulgaris 211/11P by combini...

Objectives: Considering the critical role of microRNAs (miRNAs) in regulation of cell activation, we investigated their role in circulating type-2 conventional dendritic cells (cDC2s) of patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from peripheral blood. A discovery c...

Genetic markers (DNA barcodes) are often used to support and confirm species identification. Barcode sequences can be generated in the field using portable systems based on the Oxford Nanopore Technologies (ONT) MinION sequencer. However, to achieve a broader application, current proof-of-principle workflows for on-site barcoding analysis must be s...

Background Type-I IFN activity is associated with pathogenesis and increased disease activity in primary Sjögren’s syndrome (pSS). In addition, deficiency for the type-I IFN receptor in mice prevents experimental-Sjögren’s syndrome. Plasmacytoid dendritic cells (pDC) are the premier type-I IFN producing immune cells and aberrances in their function...

Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and dryness of mouth and eyes. T and B lymphocytes that infiltrate the salivary glands play a central role in local production of autoantibodies and cytokines, associated with dryness and tissue-damage. Type-...

Objective: A considerable body of evidence supports a role for type-I IFN in the pathogenesis of primary SS (pSS). As plasmacytoid dendritic cells (pDCs) are a major source of type-I IFN, we investigated their molecular regulation by measuring expression of a large set of miRNAs. Methods: pDCs were isolated from peripheral blood of pSS patients...

Objectives Systemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy and fibrosis in skin and internal organs. Type I interferon signature found in SSc propelled us to study plasmacytoid dendritic cells (pDCs) in this disease. We aimed to identify candidate pathways underlying pDC aberranci...

Genetic markers (DNA barcodes) are often used to support and confirm species identification. Barcode sequences can be generated in the field using portable systems based on the Oxford Nanopore Technologies (ONT) MinION platform. However, to achieve a broader application, current proof-of-principle workflows for on-site barcoding analysis must be st...

Little information is available on the Citrus genus and its relatives with regard to their ability to tolerate oxygen deficiency, establishing physiological and structural modifications. In order to gain insight into how citrus rootstocks respond to low-oxygen stress, a transcriptomic analysis (using a custom microarray) was performed on Carrizo ci...

Background and objective Systemic sclerosis (SSc) is a severe autoimmune disease, in which the pathogenesis is dependent on both genetic and epigenetic factors. Altered gene expression in SSc monocytes, particularly of interferon (IFN)-responsive genes, suggests their involvement in SSc development. We investigated the correlation between epigeneti...

TLR4 activation initiates a signaling cascade leading to the production of type I IFNs and of the downstream IFN-stimulated genes (ISGs). Recently, a number of IFN-induced long non-coding RNAs (lncRNAs) that feed-back regulate the IFN response have been identified. Dysregulation of this process, collectively known as the “Interferon (IFN) Response,...

INTRODUCTION: Neutropenia represents the most frequent clinical manifestation in T-Large Granular Lymphocytes Leukemia (T-LGLL) patients. Literature data provided evidence of the involvement of soluble Fas Ligand (sFasL) in this process. Consistently, we confirmed that neutropenic T-LGLL patients were characterized by higher levels of sFasL than no...

An appropriate immune response requires a tight balance between pro- and anti-inflammatory mechanisms. IL-10 is induced at late time-points during acute inflammatory conditions triggered by TLR-dependent recognition of infectious agents and is involved in setting this balance, operating as a negative regulator of the TLR-dependent signaling pathway...

Objective The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical p...

Background: Histone deacetylase inhibitors (HDACi) suppress cytokine production in immune and stromal cells of patients with rheumatoid arthritis (RA). Here, we investigated the effects of the HDACi givinostat (ITF2357) on the transcriptional and post-transcriptional regulation of inflammatory markers in RA fibroblast-like synoviocytes (FLS). Met...

Objective: To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation. Methods: miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + AP...

Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and dryness of mouth and eyes. Classical dendritic cells are very potent antigen presenting cells known to induce strong T-cell proliferation and cytokine production. Objectives Considering the critical role...

Background Systemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy, and fibrosis in skin and internal organs. The type I IFN signature found in SSc propelled us to study plasmacytoid dendritic cells (pDCs) in this disease. Objectives To identify candidate pathways underlying pDC aberranc...

Background Primary Sjögren’s syndrome is an autoimmune disease characterised by lymphocytic infiltration of the exocrine glands and dryness of mouth and eyes. Type-I interferons (IFN) are thought to play an important role in pSS pathogenesis and plasmacytoid dendritic cells (pDCs) are capable of producing high levels of IFN. These cells infiltrate...

Background Control of cytokine mRNA degradation acts as an essential check-point to limit the overproduction of inflammatory proteins.¹ In rheumatoid arthritis (RA), altered expression of the mRNA-degrading protein TTP (tristetraprolin, ZFP36) has been recently reported in synovial tissue, possibly contributing to the perpetuating inflammatory loop...

Background: Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice. Methods: The eighty most extreme responders and non-responders to...

Background/purpose Dendritic cells (DC) are key cells in the pathogenesis of autoimmune diseases by potently activating T-cells. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are characterised by an IFN signature, caused by elevated levels of IFNα. Plasmacytoid DC (pDC) are held responsible for the increased levels of IFNα...

Background Considering the important role of miRNAs in the regulation of post–transcriptional expression of target genes, we investigated circulating small non-coding RNAs (snc)RNA levels in patients with primary Sjögren’s syndrome (pSS). In addition we assessed if serum sncRNA levels can be used to differentiate patients with specific disease feat...

Correlation between array and single RT-qPCR results in the discovery cohort. Correlation between Crt in profiling array and CT measured with single-assay Taqman RT-qPCR in patients and controls from the discovery cohort (n = 30). Spearman’s correlation coefficients (ρ) and p-values are shown. Correlations that are significant at p<0.05 are depicte...

Comparison between global mean and spike-in normalization in the discovery cohort. Results are expressed as mean FC. Differences between groups that met the threshold for the corresponding analysis (FC difference of ≤0.5 or ≥2.0 at p-value of p<0.05) are indicated in bold. Mann–Whitney U test was used to test all comparisons. (DOCX)

Differences between SSA/SSB positive and negative pSS patients in circulating sncRNA abundance. sncRNAs were measured using RT-qPCR in all pSS patients from the discovery and validation cohort (n = 37). Fold changes (FC) were calculated as compared to the mean of the healthy control group in the corresponding cohort. Results are expressed in FC as...

Purpose: The cause of noninfectious uveitis (NIU) is poorly understood but is considered to be mediated by a complex interplay between genetic, environmental, and-relatively unexplored-epigenetic factors. MicroRNAs (miRNAs) are noncoding small RNAs that are important epigenetic regulators implicated in pathologic signaling. Therefore, we mapped th...