Science Updates October 2016

Josiah Martinez
Josiah Martinez

Science news for October 2016, worldwide.

The historic $2 billion Hong Kong IPO for China Resources Pharma Group will start taking orders on October 13, price on October 20 and begin trading on October 28 (see story). CR Pharma, a subsidiary of state-owned China Resources Holdings, will set a record for the largest-ever Hong Kong IPO of a pharmaceutical company. It is the second largest China pharma in terms of revenues, behind only Sinopharm, another state-owned company.
The Jackson Laboratory, a large, unaffiliated US medical research group, expects to form a significant genomics collaboration with three groups in Wenzhou, a prefecture-level city in China's southeastern Zhejiang province (see story). In its first phase, the new collaboration will hire 75 to 100 employees and start genomics research collaborations with other organizations. In its second phase, the group would build labs in Wenzhou and hire an additional 300 to 500 employees. The Wenzhou collaboration will focus on genomic propensities for disease and will work to discover individualized therapies for cancer, heart disease and other afflictions.
archive.is/vtAJc

Next-generation sequencing (NGS) has rapidly replaced Sanger sequencing as the method of choice for diagnostic gene-panel testing. For hereditary-cancer testing, the technical sensitivity and specificity of the assay are paramount as clinicians use results to make important clinical management and treatment decisions. There is significant debate within the diagnostics community regarding the necessity of confirming NGS variant calls by Sanger sequencing, considering that numerous laboratories report having 100% specificity from the NGS data alone. Here we report our results from 20,000 hereditary-cancer NGS panels spanning 47 genes, in which all 7845 nonpolymorphic variants were Sanger- sequenced.
Of these, 98.7% were concordant between NGS and Sanger sequencing and 1.3% were identified as NGS false-positives, located mainly in complex genomic regions (A/T-rich regions, G/C-rich regions, homopolymer stretches, and pseudogene regions). Simulating a false-positive rate of zero by adjusting the variant-calling quality-score thresholds decreased the sensitivity of the assay from 100% to 97.8%, resulting in the missed detection of 176 Sanger-confirmed variants, the majority in complex genomic regions (n = 114) and mosaic mutations (n = 7).
The data illustrate the importance of setting quality thresholds for panel testing only after thousands of samples have been processed and the necessity of Sanger confirmation of NGS variants to maintain the highest possible sensitivity.

Here we describe the largest study to date, with 20,000 hereditary-cancer panel samples analyzed by NGS and nearly 8000 variants Sanger-confirmed.
Our data illustrate that a conservative quality threshold for high-confidence NGS calls is a minimal read depth coverage of >100× and a variant allele frequency (or heterozygous ratio) of >40%.
The calls satisfying these thresholds are confident to be reported out by NGS without secondary confirmation. Variant calls not meeting these metrics should be Sanger-sequenced to ensure the highest possible sensitivity and specificity of the assay. Importantly, these proper thresholds can be achieved only after the processing of thousands of samples because clinically relevant variants are extremely rare.
archive.is/tGpVS

In China, under ethical test approval, we will see begin in a matter of weeks the first course of CRISPR-Cas9 gene therapy ever administered. Led by Lu Yuo at Sichuan University’s West China Hospital, the clinical trial will make lung cancer its initial target, following up on work by immunotherapy researcher Carl June. And it is not only degenerative diseases that CRISPR fits into its ambitious crosshairs of possibility, but all manner of illness. June’s own scholarship has been concerned primarily with the possibilities of gene editing to cure autoimmune disorders such as HIV. Optometrists are among those who have seen as much cause as anyone to feel liberated by the forthcoming arrival of CRISPR as a widely used therapy. According to IOVS, due to the ease of access to DNA in the cells of the eye, gene editing to combat eye-specific conditions has been successful in around 84 per cent of trials, and is already being lined up by firms including Editas Medicine (a private medical company in Massachusetts, USA) as a prospective treatment for certain forms of blindness.
archive.is/AwEvW

Aaron White
Aaron White

3

Landon Brooks
Landon Brooks

5

Nolan Gomez
Nolan Gomez

7

Elijah Ortiz
Elijah Ortiz

4

Parker Roberts
Parker Roberts

9

Cooper Murphy
Cooper Murphy

11

Tyler Rivera
Tyler Rivera

6

Michael Miller
Michael Miller

6

Landon Walker
Landon Walker

2

Samuel Peterson
Samuel Peterson

8

Luke Hernandez
Luke Hernandez

wew

Gabriel Jones
Gabriel Jones

wew

Kayden Flores
Kayden Flores

1

Hunter Reed
Hunter Reed

2

Jordan Morris
Jordan Morris

3

Wyatt Gonzalez
Wyatt Gonzalez

4

Leo Wood
Leo Wood

5

Benjamin Perez
Benjamin Perez

6

Christopher Rogers
Christopher Rogers

7

David Martin
David Martin

8

Henry Edwards
Henry Edwards

9

Jordan Jones
Jordan Jones

10