Monthly Archives: March 2017

Reproducibility of computational workflows is automated using continuous analysis

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Our next meeting will be at 3:00 on March 24th, in room 4160 of the Discovery building. Our Selected paper is Reproducibility of computational workflows is automated using continuous analysis.
The abstract is as follows.

Replication, validation and extension of experiments are crucial for scientific progress. Computational experiments are scriptable and should be easy to reproduce. However, computational analyses are designed and run in a specific computing environment, which may be difficult or impossible to match using written instructions. We report the development of continuous analysis, a workflow that enables reproducible computational analyses. Continuous analysis combines Docker, a container technology akin to virtual machines, with continuous integration, a software development technique, to automatically rerun a computational analysis whenever updates or improvements are made to source code or data. This enables researchers to reproduce results without contacting the study authors. Continuous analysis allows reviewers, editors or readers to verify reproducibility without manually downloading and rerunning code and can provide an audit trail for analyses of data that cannot be shared.

We welcome all who can join us for this discussion. Feel free to begin that discussion in the comments section below.

Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways

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Our next meeting will be at 3:00 on March 10th, in room 4160 of the Discovery building. Our Selected paper is Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.
The abstract is as follows.

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson’s disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To “humanize” this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy.

We welcome all who can join us for this discussion. Feel free to begin that discussion in the comments section below.