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AACR Recap: Cancer Transcriptomes and a Moonshot Initiative

Tuesday, May 31, 2016

The PacBio team headed to New Orleans this past April to take in all the exciting new research presented at the American Association for Cancer Research Annual Meeting, show off our new Sequel instrument, and of course enjoy some crawfish and beignets!

On the first day of the conference, we had the pleasure of hearing a talk from last year’s AACR “What Will You Discover About Cancer?” SMRT Grant winners, Malgorzata Komor and Remond Fijneman from the Netherlands Cancer Institute. Malgorzata discussed her work to identify novel biomarkers to identify precursor lesions in colorectal cancer, which can be integrated into the fecal immunochemical test (FIT) used by the Dutch national health system. While the current FIT has useful sensitivity for cancer, it is only 27% sensitive for precancerous lesions. In order to uncover new biomarkers, they are mining mass spectrometry data from patient samples. However, ~50% of the spectra cannot be matched back to a known protein. In order to augment standard protein databases with peptides that may be present in precancerous cells, they have undertaken transcriptome sequencing of cell lines with disrupted splicing machinery. While they used both short-read and PacBio sequencing, they found that the Iso-Seq method particularly excelled at uncovering skipped and retained exon events. A number of the mis-splicing events found from RNA sequencing were confirmed to be translated by mass spectra. They plan to further investigate their biomarker candidates by screening additional patient samples.

Later in the session, we heard from Maria Nattestad, who discussed her work analyzing the genome and transcriptome of the breast cancer cell line SK-BR3 with PacBio long-read sequencing. In addition to presenting a compelling assembly and overview of the whole transcriptome results, she delved into the details of the extensive rearrangements of the Her2 gene in this highly aneuploid metastatic cell line. She described the use of two new software tools, Sniffles and SplitThreader, to confirm rearrangement events by split-read analysis and to visualize and explore the connectivity of the cancer genome and understand the natural history of complex structural variants.

We also saw a range of posters featuring PacBio long-read sequencing throughout the week, including posters on long-read sequencing from FFPE samples, the methylation profiles of Heliobacter pylori strains linked to gastric cancer, B-cell receptor signaling in non-GCB DLBCL, and targeted capture of 6 kb fragments for cost-effective detection and haplotype resolution of somatic cancer variants.

Finally, in a much-anticipated address at the close of the conference, Vice President Joe Biden shared his vision for a cancer moonshot with AACR attendees. He pledged to “make a decade’s worth of progress in five years” and shared ideas for accelerating the pace of research that had coalesced over the past year spent speaking to a wide range of scientists and leaders in the cancer research community. Biden has picked up the call for a number of reformist ideas that have been gaining traction in recent years within scientific community: incentivizing the sharing of data, getting publicly funded results out from behind pay walls, simplifying the grant application process, and funding reproducibility studies. With a goal of allocating $800 million in new funding for his initiative, including $600 million for the National Cancer Institute, Biden’s ideas for removing some of the inefficiencies of our science infrastructure should have some heft behind them. He also highlighted a number of research areas as priorities for new funding, including enhanced and early detection technology, cancer vaccine development, cancer immunotherapy and combination therapy, genomic analysis of tumor and surrounding cells, and pediatric cancer research.

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