Biology subjects

Conte, N.

Publications and source records attributed to Conte, N..

4 recordsLinked to original sources

bioRxiv2025

Conjugates of α-d-Galp-(1->3)-β-d-Galp for the serological diagnosis of Chagas disease.

BackgroundChagas disease (ChD), caused by the parasitic protozoan Trypanosoma cruzi, is a lifelong, neglected tropical disease with substantial medical and socioeconomic impact. Despite this situation, currently available diagnostic and therapeutic methods display serious limitations. A promising strategy to improve ChD serodiagnosis involves targeting parasite carbohydrate antigens, particularly the -galactosyl-rich mucins that coat the surface of bloodstream trypomastigotes (tGPI-mucins). Methods/Principle FindingsHere, we present a concise and efficient protocol for the chemical synthesis of a tGPI-mucin-derived glycotope, the disaccharide -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, and its functional conjugation to different scaffolds using the squarate method. A neoglycoprotein made upon a bovine serum albumin (BSA) carrier decorated with [~]28 units of the disaccharide, termed BSA-Di, was interrogated with sera of chronic ChD patients and healthy individuals from Argentina using an in-house enzyme-linked immunosorbent assay (ELISA). BSA-Di exhibited excellent sensitivity and effectively discriminated between ChD-positive and negative sera with high accuracy (AUC = 0.905), though its specificity was partially affected by cross-reactivity of some non-ChD sera containing natural -Gal antibodies. Conjugation of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp to T. cruzi antigenic peptides, instead of BSA, corroborated these findings and enabled the generation of bivalent ChD diagnostic reagents combining glycan- and peptide-based epitopes. Conclusions/SignificanceOverall, our results identify -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp as a robust and reliable biomarker of T. cruzi infection. The methodologies and tools described here, together with optimized derivatives, are expected to positively impact ChD serological applications. AUTHOR SUMMARYDespite the enormous burden imposed by Chagas disease, diagnostic and therapeutic methods still present serious deficiencies. Towards filling this gap, we herein developed a protocol for the chemical synthesis of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, a major glycotope present on the Trypanosoma cruzi surface coat. This disaccharide was conjugated with different molecular scaffolds and serologically evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). Our results indicate that -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp provides an overall robust and reliable biomarker of T. cruzi infection, with excellent sensitivity and only minor concerns regarding its potential cross-reactivity with natural -Gal antibodies. These findings indicate that the tools developed here, as well as optimized versions derived from them, should have a positive impact on the diagnosis and clinical management of Chagas disease and on the identification and/or clinical validation of novel drug/vaccine candidates for the treatment of T. cruzi infections.

microbiology↗

bioRxiv2023

Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer PDXs

AO_SCPLOWBSTRACTC_SCPLOWPatient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cancer cell lines (CCLs) and organoids - in terms of structural complexity, heterogeneity, and stromal interactions. We characterised 231 colorectal cancer PDXs at the genomic, transcriptomic, and epigenetic level and measured their response to cetuximab, an EGFR inhibitor in clinical use for metastatic colorectal cancer. After assessing PDXs quality, stability, and molecular concordance with publicly available patient cohorts, we trained, interpreted, and validated an integrated ensemble classifier (CeSta) which takes in input the PDXs multi-omic characterisation and predicts their sensitivity to cetuximab treatment (AUROC > 0.9). Our study shows that large PDX collections can be used to train accurate, interpretable models of drug sensitivity, which 1) better recapitulate patient-derived therapeutic biomarkers than other models trained on CCL data, 2) can be robustly validated across independent PDX cohorts, and 3) can be used for the development of novel therapeutic biomarkers.

bioinformatics↗

bioRxiv2018

PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

Patient-derived tumor xenograft (PDX) mouse models are a versatile oncology research platform for studying tumor biology and for testing chemotherapeutic approaches tailored to genomic characteristics of individual patients tumors. PDX models are generated and distributed by a diverse group of academic labs, research organizations, multi-institution consortia, and contract research organizations. The distributed nature of PDX repositories and the use of different standards in the associated metadata presents a significant challenge to finding PDX models relevant to specific cancer research questions. The Jackson Laboratory and EMBL-EBI are addressing these challenges by co-developing PDX Finder, a comprehensive open global catalog of PDX models and their associated datasets. Within PDX Finder, model attributes are harmonized and integrated using a previously developed community minimal information standard to support consistent searching across the originating resources. Links to repositories are provided from the PDX Finder search results to facilitate model acquisition and/or collaboration. The PDX Finder resource currently contains information for more than 1900 PDX models of diverse cancers including those from large resources such as the Patient-Derived Models Repository, PDXNet, and EurOPDX. Individuals or organizations that generate and distribute PDXs are invited to increase the \"findability\" of their models by participating in the PDX Finder initiative at www.pdxfinder.org.

cancer biology↗

bioRxiv2017

Identifiers for the 21st century:How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data

In many disciplines, data is highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline ten lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers; we also outline important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.

bioinformatics↗