Recognizing that pharmaceutical companies increasingly require genomics services for their research and clinical trials, contract research organization WuXi AppTec has established a genome center to serve their needs, and plans to expand the center later this year.
According to Hongye Sun, vice president of technology platform at WuXi AppTec and chief operating officer of the WuXi Genome Center, which has locations in Shanghai and Philadelphia, the genomics operation has "great synergy" with other units within the company, for example in oncology and infectious disease.
WuXi AppTec was founded in China in 2000 as WuXi PharmaTech, offering mostly chemistry services at the time. In 2008, WuXi acquired AppTec, a US-based company with several facilities, and changed its name to WuXi AppTec.
Besides manufacturing services, WuXi AppTec, which has about 7,000 employees, offers a variety of contract research and development services, including drug discovery, preclinical development, and clinical testing.
Sun joined the company in mid-2011 to build WuXi's genome center, after working at Life Technologies, and prior to that at Applied Biosystems, for almost 11 years, most recently as the project leader on Life Tech's Starlight single-molecule sequencing technology.
The genome center currently offers a variety of sequencing services, including whole-genome sequencing, exome sequencing, targeted deep sequencing, amplicon sequencing, transcriptome sequencing, metagenomic sequencing, epigenetic sequencing, microRNA sequencing, ChIP-sequencing, and DNA methylation sequencing. Also available are Affymetrix microarray services.
The center's Shanghai facility is equipped with two Illumina HiSeq 2000s, two HiSeq 2500s, and four MiSeq sequencers, as well as one Ion Torrent PGM. By the end of the year, the lab plans to add several HiSeq 2000 and Ion Proton instruments and to increase the number of staff scientists. Going forward, it would like to use the Ion Proton for "cheaper and faster" whole-genome sequencing and RNA-seq, Sun said.
In anticipation of a greater focus on clinical sequencing in the future, the lab is in the process of becoming CLIA-certified. It already has the required quality management systems in place and finished validation of an Illumina-supported cancer panel assay last October. Right now, the lab is waiting for its CLIA audit, which was originally scheduled for mid-March but has been delayed because the recent US budget cuts have prevented the auditors from traveling to China.
Sun said the HiSeq 2000 is mostly used for whole-genome sequencing, exome sequencing, metagenomic sequencing, and transcriptome sequencing, using 2x100 base pair reads, while customers have requested the HiSeq 2500 for medium-throughput sequencing projects that require fast turnaround times and longer read lengths of 2x150 base pairs, for example de novo bacterial sequencing. WuXi currently uses the MiSeq for clinical amplicon deep sequencing, for example of viruses, and for other viral sequencing projects. The PGM is also used for viral genome sequencing, as well as for cancer panels and customized panel sequencing "with the fastest turnaround time," Sun said.
The genome center's Philadelphia site has an Ion Proton installed, which it currently uses for biologics testing, such as detecting viruses in a master cell bank, culture media, and vaccines. In the future, besides providing additional sequencing services, it may process samples from US customers prior to shipping them to the Shanghai lab.
The company also provides a "full spectrum" of bioinformatics analysis services that are "highly customized" for each project, though it does not offer de novo assembly of whole human genomes at the moment. Its current compute infrastructure allows it to analyze human genome resequencing data at 40x coverage in a single day.
Since many of its customers are concerned about the security of cloud-based data delivery, project data are usually delivered on a hard disk. Since both FedEx and UPS have centers in Shanghai and the lab is located in the city's free trade zone, data shipment has not been an issue for international customers, Sun said.
About 90 percent of the genome center's customers are from the US, most of them pharmaceutical companies. Much of the remaining business comes from China, mostly from research projects at the moment, though Sun said the clinical market in China is poised to grow. "I think the big pharmas pay a lot of attention to doing clinical trials in China," he said, adding that with a CLIA sequencing lab, WuXi will be "well-positioned."
The genome center works closely with other units within WuXi AppTec. For example, for its oncology business unit, it has genotyped more than 200 patient-derived xenograft mouse models by deep exome sequencing. The models cover the major cancer types in China, and the sequencing project involved a new algorithm to filter out contaminating mouse sequencing data. As a result of this project, the oncology unit is now able to provide customers with additional information for selecting the best mouse model for drug testing.
In collaboration with WuXi AppTec's infectious disease business unit, the genome center also offers viral deep sequencing services and has developed data analysis methods for that application. It recently completed targeted deep virus sequencing of more than 1,000 patient samples for several clinical studies sponsored by an undisclosed US pharmaceutical company, which involved the MiSeq platform.
Sun said that another large US pharmaceutical company plans to award WuXi AppTec a contract for a genomic biomarker study that will involve more than 100 patients and include sample collection, DNA extraction, sequencing, and patient follow-up, though he declined to name the customer.
Recently, the genome center also started a collaboration with several Chinese universities and their affiliated hospitals to develop cancer panels specifically tailored to Chinese cancer patients, a project that will take several years.
On the research side, the center has developed a proprietary library preparation method that reduces GC bias for DNA samples with high GC content. It has applied the method in a research project for drug discovery startup WarpDrive Bio to sequence more than 500 GC-rich microbial genomes.
In addition, the center is developing a proprietary method, which it is in the process of patenting, for targeted cancer gene sequencing that combines detection of hotspot mutations, fusion genes, and copy number variations.
WarpDrive Bio has worked with the WuXi genome center for about a year, receiving "a lot of data" from them. WuXi has done "very good work for us to our specifications," said Keith Robison, a principal scientist at the firm.
Most of the DNA sequenced for WarpDrive is from bacteria with 73 percent GC content, "and WuXi has handled this well, giving us pretty good sequencing results and large amounts [of data]," Robison said in an e-mail. These included runs on the HiSeq 2000, HiSeq 2500, and MiSeq.
Pricing is "fair," with library construction costs lower and sequencing flowcell costs higher than average, and price per base "probably in line or better than most places," he said.
The company has also been "always upfront" about failed runs, which Robison said occur "with anyone doing NGS," and has kept his group well informed about project progress.
Working with a provider based in China has "some interesting aspects," he said, such as having to ship samples dried down rather than on dry ice, which is only possible to Hong Kong, and the fact that China has a number of long holidays that need to be taken into account for shipments. After those holidays, samples can also be held up in customs due to backlog, he said.
In the clinical sequencing space, a major competitor for WuXi is the Covance Genomics Laboratory, which is based in Seattle, Sun said.
In China, WuXi also competes with BGI, however mostly for research rather than clinical projects at the moment. While BGI is getting stronger in clinical applications – last year, it spun out BGI Health, which is developing diagnostic sequencing tests and plans to offer clinical sequencing services – Sun believes WuXi will remain a strong contender.
"We have worked with all the big pharmas for over 10 years," he said, and have "earned their trust" regarding data and IP protection. In addition, as part of a larger CRO, WuXi's genome center offers more than just sequencing services. However, he said, "competition is always good to make both of us better."