Biology subjects

Morabito, S.

Publications and source records attributed to Morabito, S..

3 recordsLinked to original sources

bioRxiv2020

Advanced Research Infrastructure for Experimentation in genomicS (ARIES): a lustrum of Galaxy experience

Background: With the introduction of Next Generation Sequencing (NGS) and Whole-Genome Sequencing (WGS) in microbiology and molecular epidemiology, the development of an information system for the collection of genomic and epidemiological data and subsequent transparent and reproducible data analysis became indispensable. Further requirements for the system included accessibility and ease of use by bioinformatics as well as command line profane scientists. Findings: The ARIES (Advanced Research Infrastructure for Experimentation in genomicS, https://aries.iss.it) platform has been implemented in 2015 as an instance of the Galaxy framework specific for use of WGS in molecular epidemiology. Here, the experience with ARIES is reported. Conclusions: During its five years existence, ARIES has grown into a well-established reality not only as a web service but as well as a workflow engine for the Integrated Rapid Infectious Disease Analysis (IRIDA) platform. In fact, an environment has been created with the implementation of complex bioinformatic tools in an easy-to-use context allowing scientists to concentrate on what to do instead of how to do it.

bioinformatics↗

bioRxiv2020

Single-soma transcriptomics of tangle-bearing neurons in Alzheimer's disease reveals the signatures of tau-associated synaptic dysfunction

Aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is closely associated with neuronal death and cognitive decline in Alzheimers disease (AD). To define the signatures that distinguish between aggregation-prone and resistant cell states in AD, we developed a FACS-based method for the high-throughput isolation and transcriptome profiling of individual cells with cytoplasmic aggregates and profiled 63,110 somas from human AD brains. By comparing NFT-bearing and NFT-free somas within and across neuronal subtypes, we identified the cell-type-specific and shared states. NFT-bearing neurons shared a marked upregulation of genes associated with synaptic transmission, including a core set of 63 genes enriched for synaptic vesicle cycle and transsynaptic signaling, whereas glucose metabolism and oxidative phosphorylation changes were highly neuronal-subtype-specific. Apoptosis was modestly enriched in NFT-bearing neurons despite the strong link between tau and cell death. Our datasets provide a resource for investigating tau-mediated neurodegeneration and a platform for biomarker and drug target discovery.

neuroscience↗

bioRxiv2019

Integrative genomics approach identifies conserved transcriptomic networks in Alzheimer’s disease

Alzheimers disease (AD) is a devastating neurological disorder characterized by changes in cell-type proportions and consequently marked alterations of the transcriptome. Here we use a data-driven systems biology approach across multiple cohorts of human AD, encompassing different brain regions, and integrate with multi-scale datasets comprising of DNA methylation, histone acetylation, transcriptome- and genome-wide association studies as well as quantitative trait loci to define the genetic architecture of AD. We perform co-expression network analysis across more than twelve hundred human brain samples, identifying robust AD-associated dysregulation of the transcriptome, unaltered in normal human aging. We further integrate co-expression modules with single-cell transcriptome generated from 27,321 nuclei from postmortem human brain to identify AD-specific transcriptional changes and assess cell-type proportion changes in the human AD brain. We also show that genetic variants of AD are enriched in a glial AD-associated module and identify key transcription factors regulating co-expressed modules. Additionally, we validate our results in multiple published human AD datasets which are easily accessible using our online resource (https://swaruplab.bio.uci.edu/consensusAD).

neuroscience↗