RESUMO
As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
Assuntos
Biologia Computacional/métodos , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Software , Interpretação Estatística de Dados , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Genômica/métodos , Humanos , Internet , Metabolômica/métodos , Proteômica/métodos , Reprodutibilidade dos Testes , Interface Usuário-ComputadorRESUMO
The administration of MPTP selectively targets the dopaminergic system resulting in Parkinsonism-like symptoms and is commonly used as a mice model of Parkinson's disease. We previously demonstrated that the neuroprotective compound Cu(II)(atsm) rescues nigral cell loss and improves dopamine metabolism in the MPTP model. The mechanism of action of Cu(II)(atsm) needs to be further defined to understand how the compound promotes neuronal survival. Whole genome transcriptomic profiling has become a popular method to examine the relationship between gene expression and function. Substantia nigra samples from MPTP-lesioned mice were evaluated using whole transcriptome sequencing to investigate the genes altered upon Cu(II)(atsm) treatment. We identified 143 genes affected by MPTP lesioning that are associated with biological processes related to brain and cognitive development, dopamine synthesis and perturbed synaptic neurotransmission. Upon Cu(II)(atsm) treatment, the expression of 40 genes involved in promoting dopamine synthesis, calcium signaling and synaptic plasticity were restored which were validated by qRT-PCR. The study provides the first detailed whole transcriptomic analysis of pathways involved in MPTP-induced Parkinsonism. In addition, we identify key therapeutic pathways targeted by a potentially new class of neuroprotective agents which may provide therapeutic benefits for other neurodegenerative disorders.
Assuntos
Dopamina/biossíntese , Intoxicação por MPTP/patologia , Fármacos Neuroprotetores/uso terapêutico , Compostos Organometálicos/uso terapêutico , Doença de Parkinson Secundária/genética , Doença de Parkinson/genética , Substância Negra/metabolismo , Transmissão Sináptica/genética , Tiossemicarbazonas/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Animais , Sinalização do Cálcio/genética , Complexos de Coordenação , Modelos Animais de Doenças , Dopamina/genética , Neurônios Dopaminérgicos/metabolismo , Intoxicação por MPTP/genética , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/patologia , Doença de Parkinson Secundária/induzido quimicamente , Substância Negra/efeitos dos fármacosRESUMO
Diagnostic tools for neurodegenerative diseases such as Alzheimer's disease (AD) currently involve subjective neuropsychological testing and specialized brain imaging techniques. While definitive diagnosis requires a pathological brain evaluation at autopsy, neurodegenerative changes are believed to begin years before the clinical presentation of cognitive decline. Therefore, there is an essential need for reliable biomarkers to aid in the early detection of disease in order to implement preventative strategies. microRNAs (miRNA) are small non-coding RNA species that are involved in post-transcriptional gene regulation. Expression levels of miRNAs have potential as diagnostic biomarkers as they are known to circulate and tissue specific profiles can be identified in a number of bodily fluids such as plasma, CSF and urine. Recent developments in deep sequencing technology present a viable approach to develop biomarker discovery pipelines in order to profile miRNA signatures in bodily fluids specific to neurodegenerative diseases. Here we review the potential use of miRNA deep sequencing in biomarker identification from biological fluids and its translation into clinical practice.