Mucaki, E.J., Shirley, B.C. and Rogan, P.K., 2020. Expression changes confirm genomic variants predicted to result in allele-specific, alternative mRNA splicing. Frontiers in Genetics, 11: 109 (https://www.frontiersin.org/articles/10.3389/fgene.2020.00109/full).
(preprint in bioRxiv, 549089 [doi: https://doi.org/10.1101/549089])
The following paper has been accepted for presentation:
“Pan-Cancer Repository of Validated Natural and Cryptic mRNA Splicing Mutations”,
Category: “Laboratory genetics and genomics”, Abstract Poster Number: 754 (link to Abstract)
Where: Exhibit hall, Washington Convention Center, ACMG Clinical Genetics Meeting in Seattle, Washington
When: April 2 – 6, 2019; Poster presentation time: Friday, 4/5 from 10:30am-12:00pm
This work will be available as an ePoster AS WELL AS being presented in printed format on a poster board during the Annual Meeting. Details to access the ePoster will be available soon.
Revised version of our review article on mRNA splicing in F1000Research has been highlighted in the Faculty of 1000 blog:
The blog entry includes links to our YouTube video:
Short version (3:42)
Long version (9:41)
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1. Subscription: MutationForecaster genome interpretation system
Automated Splice Site and Exon Definition Analysis Server (ASSEDA)
ASSEDA has been incorporated into Cytognomix’s MutationForecaster system. ASSEDA is described in Prediction of Mutant mRNA Splice Isoforms by Information Theory-Based Exon Definition by Mucaki et al. 2013.
Shannon pipeline for mRNA splicing and transcription factor binding site mutation analysis (SP)
SP has been incorporated into Cytognomix’s MutationForecaster system. SP for splicing mutations is described in Interpretation, Stratification and Evidence for Sequence Variants Affecting mRNA Splicing in Complete Human Genome Sequences (Shirley et al. 2013), for transcription factor binding sites in Mucaki et al. 2016, Caminsky et al. 2016, and Lu et al. 2016.
Veridical, for verification of predicted mRNA splicing mutations
Veridical sets the standard for evidence-based, statistical validation of mutation predictions from the Shannon pipeline – or other sources. Veridical has been incorporated into the MutationForecaster system. Veridical is described in Validation of predicted mRNA splicing mutations using high-throughput transcriptome data by Viner et al. 2014.
Variant effect predictor (VEP)
Predict of the effect of variants on coding regions of genes and protein sequence. SIFT and PolyPhen scores are also generated.
Cytognomix user variation database (CUVD)
Store results generated by any of our web tools at the click of a button for variants present in your sample. Variants can be directly related to public data in HGNC, NCBI, EBI, ClinVar, as well as locus specific databases. Based upon the Leiden Open Variation Database.
Cytogenetic Visual Analytic Decision Support Tool (CVDST)
Link literature evidence for gene mutations detected with VEP and SP with this tool. View your results from these other tools with our built-in genome browser. This tool also provides tracks for Cytognomix FISH probes and capture reagents.
After registration with MutationForecaster, subscriptions can be activated through the Account menu on the system.
2. Reagents: BRCA complete gene sequence capture enrichment for next generation sequencing
Capture the complete sequences of 21 genes that are mutated in women at high risk for developing breast or ovarian cancer. Derived with Cytognomix’s patented ab initio probe technology. Performance of these products for capturing exonic, intronic, upstream and downstream sequences has been established in multiplexed NGS. Contact us at the address below for a quote. Data generated with these reagents are analyzed with Cytognomix’s companion software products.
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Software that accelerates the cytogenetic biodosimetry of exposures to various qualities of radiation. The software fully automates the dicentric chromosome (DC) analysis from blood and integrates dose assessment. It has been developed for multiple individuals exposed in mass casualty or moderate scale industrial radiation events, but also can be effectively used to quickly analyze accidents involving one or a few individuals. ADCI offers speed, accuracy, and scalability that solves the challenges that users face to meet the productivity requirements for a mass casualty event. It enables greater standardization between laboratories, while still allowing different labs to customize their own calibration curves for determining unknown radiation exposures, which addresses differences in chromosome preparation methods and radiation calibration sources between labs.
4. Single copy genomic probes: FISH and genomic microarrays
Single copy FISH probes and genomic microarrays may be purchased upon request.
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“Prediction of mutant mRNA splice isoforms by information theory-based exon definition,” by Eliseos Mucaki, Ben Shirley and Peter Rogan has been accepted for publication by the journal Human Mutation.
Abstract. Mutations that affect mRNA splicing often produce multiple mRNA isoforms, resulting in complex molecular phenotypes. Definition of an exon and its inclusion in mature mRNA relies on joint recognition of both acceptor and donor splice sites. This study predicts cryptic and exon skipping isoforms in mRNA produced by splicing mutations from the combined information contents (Ri, which measures binding site affinity) and distribution of the splice sites defining these exons. The total information content of an exon (Ri,total) is the sum of the Ri values of its acceptor and donor splice sites, adjusted for the distance separating these sites, ie. the gap surprisal. Differences between total exon information contents (ΔRi,total) are predictive of the relative abundance of these exons in distinct processed mRNAs. Constraints on splice site and exon selection are used to eliminate non-conforming and poorly expressed isoforms. Molecular phenotypes are computed by the Automated Splice Site and Exon Definition Analysis server (ASSEDA; http://splice.uwo.ca). Predictions of splicing mutations were highly concordant (85.2%; n=61) with published expression data. In silico exon definition analysis will contribute to streamlining assessment of abnormal and normal splice isoforms resulting from mutations.
Update: The paper is now available online from the Journal website: DOI: 10.1002/humu.22277 and is cited on PubMed.
Update 2: John Mucaki has produced a Video Tutorial on using the ASSEDA server on YouTube.
Update 3: The accepted paper has now been copyedited, typeset and published online: http://onlinelibrary.wiley.com/doi/10.1002/humu.22277/abstract. Supplementary data are available as well. (2-21-2013)
Update 4: Annual subscriptions to the Automated Splice Site and Exon Definition server are available through Cytognomix (2-22-2013).
Update 5: The paper has been highlighted in the April 2013 issue of the Journal, where it appeared. Bing Yu, University of Sydney, authored the commentary (Vol 34, page v).
Update 6: Mucaki EJ., Shirley BC, and Rogan PK. Prediction of Mutant mRNA Splice Isoforms by Information Theory-Based Exon Definition has been published in print. Human Mutation, April 2013, Volume 34 (4), pages 557–565. The journal has made the paper FREE for anyone to download.
Links to the latest CytoGnomix products:
Applications and consulting in Geostatistical Epidemiology
Monitoring and discriminating infectious disease hotspots from high disease burden regions, eg. for COVID-19:
Zenodo repository: Geostatistical Analysis of SARS-CoV-2 Positive Cases in the United States
Defence Canada IDEaS project: Locating emerging COVID19 hotspots in Ontario after community transmission by time-correlated, geospatial analysis
Addressing large scale radiation incidents and accidents:
Article in PLOS One: Meeting radiation dosimetry capacity requirements of population-scale exposures …. (Funded by High performance computing consortium: SOSCIP and CytoGnomix)
Large scale Radiation Biodosimetry
Capacity of supercomputer version of Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI) software: Automated Cytogenetic Biodosimetry at Population-Scale and Radiation, in press.
Scalable, democratized access to ADCI:
ValidSpliceMut: A GA4GH-compliant beacon of validated splicing mutations
Article in F1000Research: Pan-Cancer repository of …..
Presentation at the 2019 American College of Medical Genetics Annual Meeting: