Publications by authors named "Michael J Purcaro"

The human genome contains ∼2000 transcriptional regulatory proteins, including ∼1600 DNA-binding transcription factors (TFs) recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled both in vitro, using techniques such as HT-SELEX, and in vivo, using techniques including ChIP-seq. We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project.

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The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth.

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The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development.

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Background: Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes.

Results: To facilitate the development of computational methods for predicting target genes, we develop a Benchmark of candidate Enhancer-Gene Interactions (BENGI) by integrating the recently developed Registry of cCREs with experimentally derived genomic interactions. We use BENGI to test several published computational methods for linking enhancers with genes, including signal correlation and the TargetFinder and PEP supervised learning methods.

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Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays.

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The relationship between neuronal activity and hemodynamic changes plays a central role in functional neuroimaging. Under normal conditions and in neurological disorders such as epilepsy, it is commonly assumed that increased functional magnetic resonance imaging (fMRI) signals reflect increased neuronal activity and that fMRI decreases represent neuronal activity decreases. Recent work suggests that these assumptions usually hold true in the cerebral cortex.

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Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness.

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Patients with epilepsy are at risk of traffic accidents when they have seizures while driving. However, driving is an essential part of normal daily life in many communities, and depriving patients of driving privileges can have profound consequences for their economic and social well-being. In the current study, we collected ictal performance data from a driving simulator and two other video games in patients undergoing continuous video/EEG monitoring.

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Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG), these changes can be characterized with high spatiotemporal resolution.

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