Greetings fellow Genomics Committee members. We hope you are enjoying some time off to unwind and enjoy the summer! We’ve had a busy spring with many accomplishments to report.

We’d like to start by congratulating the team of organizers for a highly successful workshop on ‘Advances and Roadblocks for the use of Genomics Data in Cancer Risk Assessment’. The meeting brought together experts from all over the world (North America, Europe and Asia) for two days of intensive discussions on toxicogenomics. The feedback we’ve received has been overwhelmingly positive, with many attendees expressing a desire for continued opportunities and future meetings to advance these data streams in regulatory toxicology. We also sincerely appreciate our host, McGill University, in the lovely city of Montreal!

Genomics Committee members also had the opportunity to participate in a workshop entitled ‘Mode of Action Approaches that Identify Genotoxic Mechanisms in Mammalian Cell Systems’ held jointly in May 2017 by HESI’s Genetic Toxicology Technical Committee and the Genetic Toxicology Association in Newark, Delaware. Genomics Committee members delivered presentations on advances in genomics in their areas, including new work toward further developing the TGx-28.65 biomarker and case studies associated with its application. The workshop provided an opportunity to forge cross-committee linkages as a result of the outstanding work of the Biomarker Qualification team.

Summertime is also a perfect time to catch up on things and to reflect on activities that occurred earlier in the year. We’ve taken this opportunity to reflect on the SWOT analysis conducted at the face to face meeting last fall. Through the SWOT analysis, one area identified for improvement was a need for avenues to increase communication among members and provide opportunities to exchange ideas. Related to this goal, we proposed a webinar series, the content and frequency of which were determined by our recent survey of our committee’s membership. As a result of your feedback, we’re thrilled to report that we’re instituting this webinar series beginning in September, which we hope will be a power tool for knowledge exchange.

Finally, we’d like to sincerely thank Susan Hester for representing our committee at the annual HESI meeting in Dublin, and presenting the committee’s work on RNA-sequencing applications in FFPE preserved tissues.
                                                             Dr. Alison Harrill, NIH/NIEHS
                                                            Dr. Carole Yauk, Health Canada
Please join us in extending a warm welcome to our newest committee members: Abcam, McGill University, Proctor & Gamble, Dupont, British Columbia Cancer Agency, and the National Cancer Institute. We look forward to working with you!
Genomics and Cancer Risk Assessment Workshop

Leadership Team: Drs. Jiri Aubrecht, Pfizer; Heidrun Ellinger-Ziegelbauer, Bayer; Alison Harrill, NIH/NIEHS; Jan Willem van der Laan, Medicines Evaluation Board; Carole Yauk, Health Canada  

This working group conducted a successful workshop on the topic of ‘ Advances and Roadblocks for Use of Genomics Data in Cancer Risk Assessment for Drugs and Chemicals ’. In an immersive 2-days, over 70 participants from across the globe and diverse sectors provided perspectives on toxicogenomics data deployment. Presentation and discussion included seven case studies on the use of toxicogenomics data to support both internal and regulatory decisions, and breakout group discussions on promises and challenges for these data streams. The workshop organizers offer their sincere gratitude to host McGill University for their hospitality and provision of the beautiful Faculty Club venue.

In addition to development of a workshop manuscript, the working group is currently in discussions around whether and how to follow up on recommendations and data gaps expressed during the meeting. We welcome your feedback and look forward to following up with workshop speakers and attendees.
Qualification of a Genomic Biomarker Approach to Provide Context to Positive Findings in in vitro Chromosome Damage Assays

Chair: Dr. Jiri Aubrecht, Pfizer

In 2017, the project team submitted a qualification package to the US FDA to consider a first ever transcriptomic biomarker for regulatory qualification. The committee’s in vitro transcriptomic biomarker-based approach provides mechanistic context to positive in vitro chromosome damage assay results and proposes its application for assessing carcinogenic risk. The transcriptomic biomarker distinguishes DNA damage-inducing (DDI) agents from non-DDI agents. This intensive effort by the committee to develop the biomarker approach and prepare the qualification package will enhance understanding and utilization of signature-based biomarkers for risk assessments. A manuscript describing the experimental work was submitted to the peer-reviewed press this summer. The project team is considering next phases of work. Also, a web tool for utilization of the TGx-28.65 biomarker for DNA damage classification has been developed and is now available at the National Toxicology Program website here .
Technical Considerations for RNA-Seq of FFPE Tissues

Chair: Dr. Susan Hester, US EPA

Beginning in 4Q 2015, the project team undertook an experimental program to evaluate the quality of RNA isolated from FFPE samples and to provide improved methods for applying RNA sequencing to archival samples. Specifically, the researched explored formalin effects on RNA-seq profiles, developed metrics for quality assessment of FFPE RNA, and investigated methods for improving quality of RNA and RNA-seq data from FFPE samples. A manuscript describing the findings will be submitted for publication in September 2017. This work was presented at an NCI meeting on biospecimens, via a poster at the 2017 Society of Toxicology meeting, and at the 2017 HESI Annual meeting. A second publication on quality metrics and additional experimental work are currently in development.  
Rodent miRNA Tissue Atlas

Chair: Drs. Brian Chorley, US EPA; Alison Harrill, NIH/NIEHS; Aaron Smith, Eli Lilly

Generation of a rodent miRs atlas was completed and the findings published in 2016 in BMC Genomics . A second phase study to investigate cellular localization of select miRs in rodent liver is currently under development. Additionally, the group has been exploring the feasibility and utility of measuring miRNAs in microphysiological systems. The committee presented a poster entitled “Applications for miRNA biomarkers in microphysiologic systems: An assessment by the HESI Genomics Committee” at a May 2017 NCATS Tissue Chips meeting. Further discussions around potential work in this area are ongoing within the work group.
Technical Evaluation of Methods for Measurement of miRNAs in Biofluids

Chairs: Drs. Philippe Couttet, Novartis, and Karol Thompson, US FDA

The findings from this multi-laboratory experimental program utilizing a drug-induced model of cardiac injury to assess multi-site variance in miRNA measurements in plasma, serum, and urine was published in Toxicological Sciences in September 2016. A second technical manuscript on issues surrounding absolute measurement of miRNAs (including approaches for determining lower limits of quantitation) is currently undergoing journal review.
Zebrafish as a Model for Assessing Transgenerational Effects

A multigenerational zebrafish study was conducted to evaluate potential transgenerational effects of drugs and chemicals in a zebrafish model. Three generations were assessed for histopathology, gene expression, and histone methylation. A draft manuscript has been prepared.

Genomics Annual Meeting 2017 
Watch out for more information regarding the Fall 2017 HESI Genomics Committee Annual Meeting taking place this October!
Committee Webinar Series
Watch out for dates and more information on our upcoming HESI Genomics Webinar. Webinars will take place quarterly to inform the committee of emerging projects and advancements.  
Smith A, Calley J, Mathur S, Qian H-R, Wu H, Farmen M, Caiment F, Bushel PR, Li J, Fisher C, Kirby P, Koeing E, Hall DG, Watson DE. (2016). “The Rat microRNA Body Atlas; Evaluation of the microRNA Content of Rat Organs through Deep Sequencing and Characterization of Pancreas Enriched miRNAs as Biomarkers of Pancreatic Toxicity in the Rat and Dog.” BMC Genomics 17.1: 694. Abstract here .
Thompson KL, Boitier E, Chen T, Couttet P, Ellinger-Ziegelbauer H, Goetschy M, Guillemain G, Kanki M, Kelsall J, Mariet C, de La Moureyre-Spire C, Mouritzen P, Nassirpour R, O'Lone R, Pine PS, Rosenzweig BA, Sharapova T, Smith A, Uchiyama H, Yan J, Yuen PS, Wolfinger R. (2016). Absolute measurement of cardiac injury-induced microRNAs in biofluids across multiple test sites. Toxicological Sciences 154(1):115–125. Abstract here.
Jackson MA, Yang L, Lea I, Rashid A, Kuo B, Williams A, Yauk CL, Fostel J. The TGx-28.65 biomarker web-based application for analysis of transcriptomics data to identify DNA damage-inducing chemicals in human cells in culture. Environmental and Molecular Mutagenesis. In press. Abstract here .
Syril Pettit, MEM, HESI Executive Director

Lauren Peel, Scientific Program Associate