Abstract
Knome took the “better, cheaper, faster” imperative that drove genome sequencing and addressed the next logical bottleneck: genome interpretation.
“It used to take months for teams to make sense of sequencing data,” Jorge Conde, co-founder and CFO of Knome, recalls. “We wanted to make interpretation scalable and available within days or hours so that as sequencing information becomes ubiquitous, it also will be relevant and accessible for nongeneticists.”
By applying its expertise in discovery services to automated analysis platforms, Knome is helping high-throughput genomics expand beyond large, well-funded, research laboratories so that precision medicine becomes the norm, rather than the exception, even for small laboratories.
Automated Analytics
To do this, Knome takes a two-pronged approach, offering both consulting and analysis tools that let researchers interpret results accurately themselves.
The research service, called knome-DISCOVERY, emerged from the desire to partner with companies that lacked in-house genome analysis expertise to address research or drug discovery questions. Typically, these are mid-cap clients that may have a few programs in clinical development and are very focused on ensuring those programs have the maximum probability of success, Conde says. Larger, well-established pharmas and biotechs also call on Knome to understand the genetic basis of a disease or therapeutic and thereby inform target discovery and patient selection for clinical trials. This information also is applied to adverse events to identify any genetic triggers for the events and identify predictive markers.
“We have developed very, very deep expertise and proprietary technology that allows us to do this analysis in a powerful and comprehensive way,” Conde says. Recently, Knome turned that internal expertise into a commercial product line to make genomic data accessible to non-genomicists.
The first model of the knoSYS™ platform, the knoSYS™ 100, was launched in late 2013 for whole gene and exome analysis. Its storage capabilities expand from 60 TB to 180 TB. The knoSYS™ 100 was followed this spring by knoSYS™ 25, a lower-throughput version for labs that run more gene panels than whole genomic analyses. Both versions support alignment, variant calling, annotation, multisample comparison, interpretation, variant classification, report content drafting and storage of human genome sequence data. This platform also helps labs store and share information regarding variants, panels, exomes and genomes.
“Our goal is for the knoSYS platform to be a turnkey system for all the steps required once the genome is sequenced,” Conde says. “We have the informatics engine to annotate the genomic variants, identify those that matter in specific diseases and create data sets to support intuitive querying.”
Labs ID'ed Pain Points
In developing the knoSYS platform, “We went to labs and asked them about their pain points in incorporating next-generation sequencing (NGS) data into their workflow,” Conde says. The lack of staff and genomic expertise to analyze the deluge of data was among the greatest challenges, along with difficulty incorporating NGS data into the existing workflow without reducing throughput.
Importantly, the platform accepts new information from the lab and integrates reference information from many third party sources, reducing the time needed to classify variants and ensuring information is up-to-date.
“The knoSYS platform was designed to be workflow-enabling. It includes a way for labs to encapsulate their expertise into in silico panels, virtualizing their work,” Conde adds. A dashboard lets users tune or accept the built-in quality control procedures to filter out variants that don't meet the lab's criteria, which leads to high call confidence in mutations.
Since 2008, the company has analyzed more than 3,000 human genomes and exomes and delivered more than 140 projects that characterize known and novel variants, for more than a dozen pharmaceutical and biotech clients.
While Knome sees some benefits to cloud computing, it also knows that many organizations prefer to work entirely behind their own firewalls. Therefore, the knoSYS platform installs within an organization's own facilities. “This simplifies technical issues, as well as such policy concerns as chain of custody,” he says.
The Future of NGS
The genome is the foundation of precision medicine. “We want to make genomics relevant to all stakeholders,” Conde says.
He predicts NGS technology will displace traditional Sanger sequencing in the near future for most purposes and provide a different, digital paradigm of how to perform genomic analysis. “With software, you digitize the problem and run all hypothetical scenarios at once. Our ambition is for any clinical research lab to be able to perform genomic-level analysis in-house.
“The future for clinical genomics is bright, although the ability of genomics to make an impact in patient diagnostics and therapeutics is at the very early stages,” Conde says.