Gaurav Kaushik | bioRxiv Science

bioRxiv2016

Heterozygous mutation to Chd8 causes macrocephaly and widespread alteration of neurodevelopmental transcriptional networks in mouse

The chromatin remodeling gene CHD8 represents a central node in early neurodevelopmental gene networks implicated in autism. We examined the impact of heterozygous germline Chd8 mutation on neurodevelopment in mice. Network analysis of neurodevelopmental gene expression revealed subtle yet strongly significant widespread transcriptional changes in Chd8+/- mice across autism-relevant networks from neurogenesis to synapse function. Chd8+/- expression signatures included enrichment of RNA processing genes and a Chd8-regulated module featuring altered transcription of chromatin remodeling, splicing, and cell cycle genes. Chd8+/- mice exhibited increased proliferation during brain development and neonatal increase in cortical length and volume. Structural MRI confirmed regional brain volume increase in adult Chd8+/- mice, consistent with clinical macrocephaly. Adult Chd8+/- mice displayed normal social interactions, and repetitive behaviors were not evident. Our results show that Chd8+/- mice exhibit neurodevelopmental changes paralleling CHD8+/- humans and show that Chd8 is a global genomic regulator of pathways disrupted in neurodevelopmental disorders.

Neuroscience↗

bioRxiv2016

Graph Theory Approaches for Optimizing Biomedical Data Analysis Using Reproducible Workflows

As biomedical data has become increasingly easy to generate in large quantities, the methods used to analyze it have proliferated rapidly. Reproducible and reusable methods are required to learn from large volumes of data reliably. To address this issue, numerous groups have developed workflow specifications or execution engines, which provide a framework with which to perform a sequence of analyses. One such specification is the Common Workflow Language, an emerging standard which provides a robust and flexible framework for describing data analysis tools and workflows. In addition, reproducibility can be furthered by executors or workflow engines which interpret the specification and enable additional features, such as error logging, file organization, optim1izations tocomputation and job scheduling, and allow for easy computing on large volumes of data. To this end, we have developed the Rabix Executora, an open-source workflow engine for the purposes of improving reproducibility through reusability and interoperability of workflow descriptions.

Bioinformatics↗