Karam, A. | bioRxiv Science

bioRxiv2019

GAD: a Python script for dividing genome annotation files into feature-based files

Nowadays, manipulating and analyzing publicly available genomic datasets become a daily task in bioinformatics and genomics laboratories. The release of several genome sequencing projects prompts bioinformaticians to develop automated scripts and pipelines which analyze genomic datasets in particular gene annotation pipelines. Handling genome annotation files with fully-featured programs used by non-developers is necessary, furthermore, accelerating genomic data analysis with a focus on diminishing the genome annotation and sequence files based on specific features is required. Consequently, to extract genome features from GTF or GFF3 in a precise manner, GAD script (https://github.com/bio-projects/GAD) provides a simple graphical user interface which interpreted by all python versions installed in different operating systems. GAD script contains unique entry widgets which are capable to analyze multiple genome sequence and annotation files by a click. With highly influential coded functions, genome features such upstream genes, downstream genes, intergenic regions, genes, transcripts, exons, introns, coding sequences, five prime untranslated regions, and three prime untranslated regions and other ambiguous sequence ontology terms will be extracted. GAD script outputs the results in diverse file formats such as BED, GTF/GFF3 and FASTA files which supported by other bioinformatics programs. Our script could be incorporated into various pipelines in all genomics laboratories with the aim of accelerating data analysis.

bioinformatics↗

bioRxiv2018

The Ciliopathy Gene Ftm/Rpgrip1l Controls Mouse Forebrain Patterning Via Region-Specific Modulation Of Hedgehog/Gli Signaling.

Primary cilia are essential for central nervous system development. In the mouse, they play a critical role in patterning the spinal cord and telencephalon via the regulation of Hedgehog/Gli signaling. However, despite the frequent disruption of this signaling pathway in human forebrain malformations, the role of primary cilia in forebrain morphogenesis has been little investigated outside the telencephalon. Here we studied development of the diencephalon, hypothalamus and eyes in mutant mice in which the Ftm/Rgprip1l ciliopathy gene is disrupted. At the end of gestation, Ftm-/- fetuses displayed anophthalmia, a reduction of the ventral hypothalamus and a disorganization of diencephalic nuclei and axonal tracts. In Ftm-/- embryos, we found that the ventral forebrain structures and the rostral thalamus were missing. Optic vesicles formed but lacked the optic cups. We analyzed the molecular causes of these defects. In Ftm-/- embryos, Sonic hedgehog (Shh) expression was lost in the ventral forebrain but maintained in the zona limitans intrathalamica (ZLI), the mid-diencephalic organizer. In the diencephalon, Gli activity was dampened in regions adjacent to the Shh-expressing ZLI but displayed a higher Hh-independent ground level in the other regions. Our data uncover a complex role of cilia in development of the diencephalon, hypothalamus and eyes via the region-specific control of the ratio of activator and repressor forms of the Gli transcription factors. They call for a closer examination of forebrain defects in severe ciliopathies and for a search for ciliopathy genes as modifiers in other human conditions with forebrain defects.

developmental biology↗