Biology subjects

Grabowicz, I. E.

Publications and source records attributed to Grabowicz, I. E..

3 recordsLinked to original sources

bioRxiv2021

A new analytical pipeline reveals metatranscriptomic changes upon high-fat diet in a Down syndrome mouse model.

The existing methods designated for metatranscriptomic studies are still rare and being developed. In this paper we present a new analytical pipeline combining contig assembly, gene selection and functional annotation. This pipeline allowed us to reconstruct contigs with very high unique mappability (83%) and select sequences encoding putative bacterial genes reaching also a very high (66%), unique mappability of the NGS sequencing reads. Then, we have applied our pipeline to study faecal metatranscriptome of a Down syndrome (DS) mouse model, the Ts65Dn mice, in order to identify the differentially expressed transcripts. Recent studies have implicated dysbiosis of gut microbiota in several central nervous system (CNS) disorders, including DS. Given that DS individuals have an increased prevalence of obesity, we also studied the effects of a high-fat diet (HFD) on the transcriptomic changes of mice gut microbiomes, as the complex symbiotic relationship between the gut microbiome and its host is strongly influenced by diet and nutrition. Using our new pipeline we found that compared to wild type (WT), Ts65Dn mice showed an elevated expression levels of genes involved in hypoxanthine metabolism, which contributes to oxidative stress, and a down-regulated expression of genes involved in interactions with host epithelial cells and virulence. Microbiomes of mice fed HFD showed significantly higher expression levels of genes involved in membrane lipopolysaccharides / lipids biosynthesis, and decreased expression of osmoprotection and lysine fermentation genes, among others. We also found evidence that mice microbiota is capable of expressing genes encoding for neuromodulators, which may play a role in development of compulsive overeating and obesity. Our results show a DS-specific metatranscriptome profile and show that a high-fat diet affects the metabolism of mice gut microbiome by changing activity of genes involved in lipids, sugars, proteins and amino acids metabolism and cell membranes turnover. Our new analytical pipeline combining contig assembly, gene selection and functional annotation provides new insights into the metatranscriptomic studies.

bioinformatics↗

bioRxiv2020

Characterization of the microbiome of Down syndrome mouse model (Ts65Dn) in standard and high-fat diet.

The intestinal microbiota is known to affect its host in numerous ways and can be altered by many factors including the host genotype and high-calorie diets. Down syndrome (DS) is a genetic neurodevelopmental disorder caused by the total or partial triplication of chromosome 21. Recently, a human study reported microbiota differences between DS and euploid humans. To further explore the differences due to the genotype, we here investigated the microbiome of trisomic mice (Ts65Dn). In trisomic mice we found a significant enrichment in abundances of bacteria: Bacteroides ovatus, B. thetaiotaomicron, and Akkermansia muciniphila - the mucus-degrading and gut-health promoting species. Since diet composition has an effect on microbiota species, we studied the effect of a high-fat diet on the observed genotypic differences. Our study provides evidence that microbiomes of trisomic mice on the control diet present more inter-individual differences than WT mice. Moreover, we observed that the high-fat diet led to increased differences between individuals and this effect was even more pronounced in the trisomic than in WT mice. We validated the results obtained with widely used 16rRNA gene sequencing with the sequencing of the total RNA. HighlightsO_LIDown syndrome (DS) model mice faecal microbiomes are characterized by an overrepresentation of Bacteroides ovatus, Bacteroides thetaiotaomicron, and Akkermansia muciniphila species. C_LIO_LIDS mice are characterized by higher heterogeneity of their microbiome communities than WT mice. C_LIO_LIHigh-fat diet leads to more diverse microbiome communities between mice, especially in trisomic genotype. C_LI

genomics↗

bioRxiv2020

Epigenetic regulation of differentially expressed genes between various glioma types

Gliomas are the most frequent primary tumors of the central nervous system (CNS) and encompass two major subgroups: diffuse, malignant gliomas and benign, well differentiated gliomas showing a more circumscribed growth. Genome-wide next generation sequencing studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different types of gliomas improving tumor diagnosis and having important implications for future clinical trials and patient management. We have recently created a unique resource encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we took advantage of a wealth of data from those high-throughput experiments, intersected those data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found a set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing glioma-related genes. Moreover, many genes associated with the cell-matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by the long range contacts with enhancers. Overall, the results presented here demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy. We demonstrated that integration of whole genome epigenetic data with Hi-C data and transcriptomic profiles described in this work, can segregate low and high grade gliomas and reveal new regulatory networks that could explain some of the functional differences between gliomas of different malignancies. HighlightsO_LIIntegration of ATAC-seq, ChIP-seq and RNA-seq reveals glioma malignancy-related gene regulatory networks. C_LIO_LITADs segmentation contributes to gene-epigenetically modified enhancer relationships. C_LIO_LIContacts of active enhancers in gliomas of different malignancies might affect expression of genes involved in cancerogenesis, such as PROTOCADHERINs or EGFR. C_LI

cancer biology↗