Browsing articles by " Peter Rogan"

September 15, 2017. Projects featured in SHARCNET community update

Sep 16, 2017   //   by Peter Rogan   //   News  //  Comments Off

SHARCNET article

September 12, 2017. New publication on cancer of unknown primary

Sep 13, 2017   //   by Peter Rogan   //   News  //  Comments Off

Hannouf MB,  Winquist E,  Mahmud SM,   Brackstone M,  Sarma S,  Rodrigues G,  Rogan PK,  Hoch JS, Zaric GS.  The clinical and economic impact of primary tumour identification in metastatic cancer of unknown primary tumour: a population-based retrospective matched cohort study, PharmacoEconomics, 2017 (doi:10.1007/s41669-017-0051-2)  Link:  pdf

Sept. 6, 2017. Article in Western News about Radiation Biodosimetry project

Sep 7, 2017   //   by Peter Rogan   //   News  //  Comments Off

WesternNewsArticleADCI2017pic

(click on article)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                         Link to Article 

September 3, 2017. New video protocol describing radiation biodosimetry software

Sep 5, 2017   //   by Peter Rogan   //   News  //  Comments Off

Download the written protocol: link

August 24, 2017. Announcement of BCIP contract to CytoGnomix by the Government of Canada

Aug 23, 2017   //   by Peter Rogan   //   News  //  Comments Off

The press event will take place at the Convergence Centre, Western Research Park, London Ontario, 24-Aug-2017 at 10:30 AM.

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August 9, 2017. Publication on improved accuracy in radiation biodosimetry

Aug 2, 2017   //   by Peter Rogan   //   News  //  Comments Off

Liu J, Li Y, Wilkins R, Flegal F, Knoll JHM, Rogan PK.  Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, F1000Research 2017, 6:1396 (doi: 10.12688/f1000research.12226.1) [preprint in bioRxiv; doi: https://doi.org/10.1101/120410].

F1000Res6_1396

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

July 12, 2017. CytoGnomix exhibiting at 2017 American Society of Human Genetics Annual Conference

Jul 12, 2017   //   by Peter Rogan   //   News  //  Comments Off

We will be exhibiting our cytogenetics and genomics products at the upcoming American Society of Human Genetics Annual Conference in Orlando, Florida (Oct 17-21, 2017). Please visit our booth or come by to ask questions our software and reagents. Talk to us about genome interpretation with MutationForecaster, radiation dose estimation with the Automated Dicentric Chromosome Identifier, or single copy reagents for NGS capture, FISH or microarrays.  We will also be presenting 3 scientific papers at the meeting.

We  welcome inquiries about joint R & D projects and partnerships.  Contact us.

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July 5, 2017. MutationForecaster®: improved documentation

Jul 5, 2017   //   by Peter Rogan   //   News  //  Comments Off

We have restructured and added new content to the MutationForecaster®  “Learn More” page:

LearnMoreUpdated

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

June 30, 2017. New publication on breast cancer genetics

Jul 1, 2017   //   by Peter Rogan   //   News  //  Comments Off

Yang et al. Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia. Breast Cancer Research and Treatment, 2017.  (Link to paper  [pdf])

This study applies information theory based mutation analysis to interpret pathogenic variants and variants of uncertain significance in these genes.

 

June 21, 2017. Landing page: Radiation.CytoGnomix.com

Jun 21, 2017   //   by Peter Rogan   //   News  //  Comments Off

Check our CytoGnomix’s new radiation biodosimetry landing page:

Capture

 

 

 

 

 

 

 

 

 

 

 

 

 

June 3, 2017. Presentation at Variant Detection 2017

Jun 3, 2017   //   by Peter Rogan   //   News  //  Comments Off

variants2017

Peter Rogan will be presenting “A Unified Framework For Prioritization Of Variants Of Uncertain Significance In Hereditary Breast And Ovarian Cancer” at Variant Detection 2017 in Santiago de Compostela Spain on June 5, 2017.

Coauthors are Eliseos Mucaki1, Natasha Caminsky1, Ruipeng Lu1, Joan Knoll1,2 and Peter Rogan1,2. 1University of Western Ontario, 2CytoGnomix Inc.

Abstract:

Purpose: A significant proportion of HBOC patients receive uninformative genetic testing results, an issue exacerbated by the overwhelming quantity of variants of uncertain significance identified. We apply information theory (IT) to predict and analyze non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. This provides a unifying framework where, aside from protein coding changes, pathogenic variants occurring within sequence elements can be prioritized based 19 on their recognition by proteins involved in mRNA splicing, transcription, and untranslated region binding and structure. To support the utilization of IT analysis, we established IT-based variant interpretation accuracy by performing a comprehensive review of mutations altering mRNA splicing in rare and common diseases1.

Methods: We captured and enriched for coding and non-coding variants in genes known or suspected to increase HBOC risk. Custom oligonucleotide baits spanning the complete coding, non-coding, and intergenic regions 10 kb up- and downstream of ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, TP53, ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2 were synthesized for solution hybridization enrichment. Aside from protein coding and copy number changes, IT-based sequence analysis was used to identify and prioritize pathogenic non-coding variants that occurred within sequence elements predicted to be recognized by proteins or protein complexes involved in mRNA splicing, transcription, and untranslated region (UTR) binding and structure. Mutation-associated affinity changes were computed in transcription factor (TFBSs)2, splicing regulatory (SRBSs)3, and RNA-binding protein (RBBSs)4 binding sites following mutation. This approach was supplemented by in silico and laboratory analysis of UTR structure.

Results: Unique and divergent repetitive sequences were sequenced in 379 high-risk, patients without identified mutations in BRCA1/2. We identified 47,501 unique variants and we prioritized 429 variants. The methods were first applied in 7 complete genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, TP53) in 102 anonymized individuals (15,311 variants)4, then validated in 287 patients in an ethics board approved study (38,372 variants)5. In the validation study, we prioritized variants affecting the strengths of 10 splice sites (4 natural, 6 cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure, and 17 for pseudoexon activation. Additionally, 4 frameshift, 2 in-frame deletions, and 5 stopgain mutations were identified. Multifactorial cosegregation analysis further reduced the set of candidate pathogenic variants in some families.

Conclusion: Complete gene sequence analysis followed by a unified framework can be used to interpret non-coding variants that may affect gene expression. When combined with pedigree information, complete gene sequence analysis can distill large numbers of VUS among a wide spectrum of functional mutation types to a limited set of variants for downstream functional and co-segregation analysis. References: 1Caminsky et al. F1000Res 3:282, 2015; 2Lu et al. Nucleic Acids Res. doi: 10.1093/nar/gkw1036, 2016; 3Mucaki et al. Hum. Mut. 34:557-565. 2013; 4Mucaki et al. BMC Med Genomics. 9:19, 2016; 5Caminsky et al. Hum. Mut. 37:640-52, 2016.

June 1, 2017. Products delivered under the Build in Canada Innovation Program

Jun 3, 2017   //   by Peter Rogan   //   News  //  Comments Off

CytoGnomix has delivered the Automated Dicentric Chromosome Identifier and Dose Estimator system to the Healthy Environments and Consumer Safety Branch at Health Canada, Government of Canada and to the Biodosimetry laboratory at Canadian Nuclear Laboratories.  Each lab received two licensed versions of the product on a state of the art MSI portable computer  and two full days of training on the systems. Experienced personnel will use ADCI to perform tests on radiation exposed blood  samples from international comparative biodosimetry exercises. They will evaluate accuracy of dose estimation and speed of analysis.   

May 22, 2017. Protocol on automated radiation biodosimetry accepted for publication

May 22, 2017   //   by Peter Rogan   //   News  //  Comments Off

JoVE

Our article:

“Expedited radiation biodosimetry by automated dicentric chromosome identification and dose estimation”

Ben Shirley 1^ , Yanxin Li 1^ , Joan H. M. Knoll 1,2 , and Peter K. Rogan 1,3

1 CytoGnomix, Departments of 2 Pathology and Laboratory Medicine and 3 Biochemistry, Western

University, London, ON Canada

has been accepted for publication in the Journal of Visualized Experiments. The paper describes, in detail, the protocol for use of the Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI). It will be accompanied by a professionally produced video that illustrates how the software is used to determine radiation dose from metaphase cell images.

Short abstract:

The cytogenetic dicentric chromosome (DC) assay quantifies exposure to ionizing radiation. The Automated Dicentric Chromosome Identifier and Dose Estimator software accurately and rapidly estimates biological dose from DCs in metaphase cells. It distinguishes monocentric chromosomes and other objects from DCs, and estimates biological radiation dose from the frequency of DCs.

May 4, 2017. CytoGnomix introducing new biodosimetry product

May 4, 2017   //   by Peter Rogan   //   News  //  Comments Off

MasterLogo-RGB  CytoGnomix will be exhibiting at the 22nd Nuclear Medical Defense Conference, next week (May 8th to 11th 2017) in Munich, Germany. We will be introducing our biodosimetry product, the Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI) at the meeting. We will also be presenting a poster on novel, patent pending methods to automatically curate metaphase cell selection and chromosomes in digital images.

ConRad2017

April 18, 2017. US Patent 9,624,549 issued about chemotherapy target identification

Apr 18, 2017   //   by Peter Rogan   //   News  //  Comments Off

US Patent 9,624,549 has been issued!
“Stable gene targets in breast cancer and use thereof for optimizing therapy. ” Peter K Rogan and Joan Knoll.    (link)

This technology is the basis of biochemically inspired chemotherapy prediction by machine learning (http://chemotherapy.cytognomix.com).

April 8, 2017. Presentation about chemotherapy outcome prediction

Apr 9, 2017   //   by Peter Rogan   //   News  //  Comments Off

Rogan PK, Mucaki EJ, Baranova K, Dorman S, Knoll JHM. Predicting responses to chemotherapies by biochemically-inspired machine learning. Innovative Approaches to Optimal Cancer Care in Canada, Canadian Partnership against Cancer, Toronto, Apr. 6-8, 2017. (Link to abstract)

March 31, 2017. New preprint on increased accuracy in radiation biodosimetry

Mar 31, 2017   //   by Peter Rogan   //   News  //  Comments Off

Accurate Cytogenetic Biodosimetry Through Automation Of Dicentric Chromosome Curation And Metaphase Cell Selection

Jin Liu, Yaking Li, Ruth Wilkins, Farrah Flegal, Joan H. M. Knoll, Peter K. Rogan.
Abstract:
Software to automate digital pathology relies on image quality and the rates of false positive and negative objects in these images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received from the frequency of DCs. We present image segmentation methods to rank high quality cytogenetic images and eliminate suboptimal metaphase cell data based on novel quality measures. Improvements in DC recognition increase the accuracy of dose estimates, by reducing false positive (FP) DC detection. A set of chromosome morphology segmentation methods selectively filtered out false DCs, arising primarily from extended prometaphase chromosomes, sister chromatid separation and chromosome fragmentation. This reduced FPs by 55% and was highly specific to the abnormal structures (≥97.7%). Additional procedures were then developed to fully automate image review, resulting in 6 image-level filters that, when combined, selectively remove images with consistently unparsable or incorrectly segmented chromosome morphologies. Overall, these filters can eliminate half of the FPs detected by manual image review. Optimal image selection and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Consequently, the average dose estimation error was reduced from 0.4Gy to <0.2Gy with minimal manual review required. These image filtering approaches constitute a reliable and scalable solution that results in more accurate radiation dose estimates.

February 27, 2017. CytoGnomix finalizes contract with Government of Canada

Feb 26, 2017   //   by Peter Rogan   //   News  //  Comments Off

CytoGnomix has finalized our contract with Public Works Government Services Canada under the Build in Canada Innovation Program. This agreement licenses the Automated Dicentric Chromosome Identifier (ADCI) to the Consumer and Clinical Radiation Protection Bureau at Health Canada and Canadian Nuclear Laboratories and provides on-site training to these labs. These biodosimetry reference labs will test the software and provide feedback. Test results will support CytoGnomix’s submitted application to the Medical Device Bureau at Health Canada.

Jan. 28, 2017. New version of F1000Research paper on chemotherapy response in breast cancer

Jan 29, 2017   //   by Peter Rogan   //   News  //  Comments Off

We have published a new version of:

Predicting Outcomes of Hormone and Chemotherapy in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) Study by Biochemically-inspired Machine Learning. F1000Research 2017, 5:2124 (doi:10.12688/f1000research.9417.2)

The revision addresses the comments of the reviewers and adds several new analyses and results. Among our findings was the discovery of significant batch effects that, respectively, differentiate gene expression of signature genes in the Discovery and Validation patient datasets. This is an important cautionary message that should be considered when analyzing the performance of any machine learning based method.

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