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Biognosys Aiming to Capitalize on Rising Interest in Data Independent Acquisition Mass Spec

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Swiss proteomics firm Biognosys is making a bet on the rise of data independent acquisition mass spec, adding last month a spectral library generation service to its offerings and expanding the capabilities of its DIA data analysis program Spectronaut to include compatibility with Thermo Fisher Scientific's Q Exactive instrument.

Although DIA mass spec approaches have existed for almost a decade, the technology has gained new momentum since AB Sciex last year introduced its Swath DIA method for use on its TripleTOF 5600+ machine (PM 6/8/2012). And while DIA has to date largely remained the province of mass spec experts and cutting edge academic proteomics labs, Biognosys is anticipating growing industry demand for the approach, Oliver Rinner, the company's managing director and chief scientific officer, told ProteoMonitor.

DIA differs from traditional shotgun proteomics in that it allows researchers to collect information on all ions in a sample.

In conventional data-dependent acquisition, the mass spectrometer performs an initial scan of precursor ions entering the instrument and selects a sampling of those ions for fragmentation and generation of MS/MS spectra. Because instruments can't scan quickly enough to acquire all the precursors entering at a given moment, however, many ions – particularly low-abundance ions – are never selected for MS/MS fragmentation and so are not detected.

In DIA, on the other hand, the mass spec selects broad m/z windows and fragments all precursors in that window, allowing the machine to collect MS/MS spectra on all of them.

The technique was initially proposed by Scripps Institute researcher John Yates III in a 2004 Nature Methods paper and became commercially available in 2006 with Waters' launch of its MSE DIA method. The launch of AB Sciex's Swath method, however, marked something of a turning point for DIA, Rinner noted, as the focus shifted from simply using the approach to generate proteomic data to analyzing that data in a targeted, quantitative manner.

As University of Washington researcher Michael MacCoss, whose lab's open-source Skyline software system has emerged as a major platform for DIA data analysis and method development, told ProteoMonitor in an interview on DIA last year, what differentiates recent techniques "is that the data analysis has changed to: Can we find peptide X in this data? As opposed to, let's try to find signals and [make peptide IDs]" (PM 6/8/2012).

Biognosys seeks to be at the forefront of this shift toward "applying a targeted proteomics approach to this DIA data," Rinner said.

In particular, said Lukas Reiter, Biognosys' head of bioinformatics, the company aims to provide tools for targeted analysis of large-scale DIA experiments – projects looking at, for instance, quantitative data on 10,000 different peptides across hundreds of different samples.

"Our focus is really to provide very powerful processing of large datasets," he told ProteoMonitor. "We are very strong in and designed for high-content DIA experiments... [where] you need a lot of automatic processing – because obviously you can't look at each individual analyte anymore – and very powerful statistics."

Biognosys was founded in 2008 as a spin-out from the lab of Swiss Federal Institute of Technology Zurich researcher Ruedi Aebersold, where Rinner and Reiter were a post-doc and graduate student, respectively. The company currently employs 12 people and is funded by a combination of angel investors and venture capital, Rinner said.

The company's Spectronaut software is based on the mProphet algorithm developed by Reiter, Rinner, Aebersold, and several other ETH Zurich collaborators. Detailed in a paper published in Nature Methods in 2011, the algorithm automates the identification of specific peptides in selected-reaction monitoring mass spec datasets by integrating multiple aspects of SRM data in a probabilistic scoring system.

Given the similarities between pulling targeted data out of large SRM datasets and pulling it out of DIA datasets, the algorithm proved suitable as a basis for Spectronaut, as well. Biognosys launched an initial version of the software supporting AB Sciex's Swath method in January and last month launched an updated version that also supports Thermo Fisher's Q Exactive.

According to Rinner, the company is looking into developing the software for use with other vendors' DIA methods, but, he noted, this will largely depend on whether it receives customer interest in doing DIA projects on these systems.

The company currently offers free licenses for the software to academic users, with the aim, Rinner said, of expanding use of the software within the field. Beyond these users, the company also has three academic groups with which it is collaborating on further development of the platform: ETH Zurich's Aebersold, Steven Carr's lab at the Broad Institute, and researchers at the Functional Genomics Center Zurich.

In addition to academics, the company has begun in the last year promoting Spectronaut and DIA mass spec to industry, selling services encompassing the entire DIA workflow, Rinner said.

"We've networked with various companies where we offered the Swath technology as a service," he said, citing ag-bio and pharma as sectors that have shown particular interest thus far.

Rinner added that the expansion into DIA work also feeds into Biognosys' SRM-MS work, which can be used for further investigation of hits identified during DIA discovery projects. SRM-MS is the company's core offering and is still the dominant mass spec method used for targeted proteomics, he noted.

"There is no question that this targeted DIA method is on the cutting edge and is opening up a lot of business opportunities in the discovery area," he said. "But we still see a lot of opportunities and potential for mass spec-based targeted proteomics in the triple quad space – [for example] all the clinical [proteomics] applications. At the moment DIA is getting a lot of attention, but there is still a lot of potential for [SRM]."

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