Biology subjects

Filosi, M.

Publications and source records attributed to Filosi, M..

5 recordsLinked to original sources

bioRxiv2024

Taxonize-gb: A tool for filtering GenBank non-redundant databases based on taxonomy

Analyzing taxonomic diversity and identification in diverse ecological samples has become a crucial routine in various research and industrial fields. While DNA barcoding marker-gene approaches were once prevalent, the decreasing costs of next-generation sequencing have made metagenomic shotgun sequencing more popular and feasible. In contrast to DNA-barcoding, metagenomic shotgun sequencing offers possibilities for in-depth characterization of structural and functional diversity. However, analysis of such data is still considered a hurdle due to absence of taxa-specific databases. Here we present taxonize-gb, a command-line software tool to extract GenBank non-redundant nucleotide and protein databases, related to one or more input taxonomy identifier. Our tool allows the creation of taxa-specific reference databases tailored to specific research questions, which reduces search times and therefore represents a practical solution for researchers analyzing large metagenomic data on regular basis. Taxonize-gb is an open-source command-line Python-based tool freely available for installation at https://pypi.org/project/taxonize-gb/ and on GitHub https://github.com/msabrysarhan/taxonize_genbank. It is released under Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

bioinformatics↗

bioRxiv2023

The interplay between oxidative stress and inflammation supports autistic-related behaviors in mice

Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental condition characterized by social communication deficits and repetitive/restricted behaviors. Several studies showed that inflammation may contribute to ASD. Here we used RT-qPCR, RNA sequencing, immunohistochemistry, and flow cytometry to show that pro-inflammatory molecules were increased in the cerebellum and periphery of mice lacking Cntnap2 (Cntnap2-/-), a robust model of ASD. In parallel, oxidative stress was present in the cerebellum of mutant animals. Systemic treatment with N-acetyl-cysteine (NAC) rescued cerebellar oxidative stress and inflammation as well as motor and social impairments in Cntnap2-/- mice. This was accompanied by improved function of microglia cells in NAC-treated mutant animals. Intriguingly, social deficits, cerebellar inflammation and microglia dysfunction were induced by NAC in Cntnap2+/+animals. Our findings therefore suggest that the interplay between oxidative stress and inflammation may support ASD-related behaviors in mice.

immunology↗

bioRxiv2023

Performing highly parallelized and reproducible GWAS analysis on biobank-scale data

MotivationGenome-wide association studies (GWAS) in large biobanks are transforming genetic research and enable the detection of novel genotype-phenotype relationships. In the last two decades, over 60,000 genetic associations across thousands of human diseases and traits have been discovered using a GWAS approach. Due to denser genotyping and increasing sample sizes, researchers are increasingly faced with computational challenges when executing GWAS analysis. A reproducible, modular and extensible pipeline with a focus on parallelization is essential to simplify data analysis and to allow researchers to devote their time to other essential tasks such as result interpretation and downstream analysis. ResultsHere we present nf-gwas, a Nextflow pipeline to run biobank-scale GWAS analysis. The pipeline automatically performs numerous pre- and post-processing steps, integrates regression modeling from the REGENIE package and currently supports single-variant, gene-based and interaction testing. nf-gwas also includes an extensive reporting functionality that allows to inspect thousands of phenotypes and navigate interactive Manhattan plots directly in the web browser. The pipeline is extensively tested using the unit-style testing framework nf-test to ensure code maintainability, a crucial requirement in clinical and pharmaceutical settings. Furthermore, we validated the pipeline against published GWAS datasets and benchmarked the pipeline on high-performance computing and cloud infrastructures to provide cost estimations to end users. Availabilitynf-gwas is free available at https://github.com/genepi/nf-gwas. Contactlukas.forer@i-med.ac.at

bioinformatics↗

bioRxiv2020

Transcriptome analysis of the zebrafish atoh7-/- mutant, lakritz, highlights Atoh7-dependent genetic networks with potential implications for human eye diseases

Expression of the bHLH transcription protein Atoh7 is a crucial factor conferring competence to retinal progenitor cells for the development of retinal ganglion cells. A number of studies have emerged establishing ATOH7 as a retinal disease gene. Remarkably, such studies uncovered ATOH7 variants associated with global eye defects including optic nerve hypoplasia, microphthalmia, retinal vascular disorders and glaucoma. The complex genetic networks and cellular decisions arising downstream of atoh7 expression, and how their dysregulation cause development of such disease traits remains unknown. To begin to understand such Atoh7-dependent events in vivo we performed transcriptome analysis of wild type and atoh7 mutant (lakritz) zebrafish embryos at the onset of retinal ganglion cell differentiation. We investigated in silico interplays of atoh7 and other disease-related genes and pathways. By network reconstruction analysis of differentially expressed genes we identified gene clusters enriched in retinal development, cell cycle, chromatin remodelling, stress response and Wnt pathways. By weighted gene coexpression network we identified coexpression modules affected by the mutation and enriched in retina development genes tightly connected to atoh7. We established the groundwork whereby Atoh7-linked cellular and molecular processes can be investigated in the dynamic multi-tissue environment of the developing normal and diseased vertebrate eye.

developmental biology↗

bioRxiv2018

The Italian Autism Network (ITAN): A Resource for Molecular Genetics and Biomarker Investigations

BackgroundA substantial genetic component accounts for Autism Spectrum Disorders (ASD) aetiology, with some rare and common genetic risk factors recently identified. Large collections of DNAs from thoroughly characterized ASD families are an essential step to confirm genetic risk factors, identify new variants and investigate genotype-phenotype correlations. The Italian Autism Network aimed at constituting a clinical database and a biorepository of samples derived from ASD subjects and first-degree relatives extensively and consistently characterized by child psychiatry centers in Italy.\n\nMethodsThe study was approved by the ethical committee of the University of Verona, the coordinating site, and by the local ethical committees of each recruiting site. Certified staff was specifically trained at each site for the overall study conduct, for clinical protocol administration and handling of biological material. A centralized database was developed to collect clinical assessment and medical records from each recruiting site. Children were eligible for recruitment based on the following inclusion criteria: age 4-18 years, at least one parent or legal guardian giving voluntary written consent, meeting DSM-IV criteria for Autistic Disorder or Aspergers Disorder or Pervasive Developmental Disorder NOS. Affected individuals were assessed by full psychiatric, neurological and physical examination, evaluation with ADI-R and ADOS scales, cognitive assessment with Wechsler Intelligence Scale for Children or Preschool and Primary, Leiter International Performance Scale or Griffiths Mental Developmental Scale. Additional evaluations included language assessment, the Krug Aspergers Disorder Index, and instrumental examination such as EEG and structural MRI. DNA, RNA and plasma were collected from eligible individuals and relatives. A central laboratory was established to host the biorepository, perform DNA and RNA extraction and lymphocytes immortalisation.\n\nDiscussionThe study has led to an extensive collection of biological samples associated with standardised clinical assessments from a network of expert clinicians and psychologists. Eighteen sites have received ADI/ADOS training, thirteen of which have been actively recruiting. The clinical database currently includes information on 812 individuals from 249 families, and the biorepository has samples for 98% of the subjects. This effort has generated a highly valuable resource for conducting clinical and genetic research of ASD, amenable to further expansion.

neuroscience↗