Recent technological advancements in high-resolution mass spectrometry (MS) have helped create a clearer and more detailed picture of biological processes. Through the enhanced elucidation of biomolecular structural information and characterization of cellular networks, MS provides more information than ever before.
With rapid growth in the volume and complexity of MS data, accurate and reproducible analysis can be challenging. The ability to acquire, analyze, manage, and report data generated in MS systems is evolving as new applications are discovered, and current uses improved. Innovations in MS software address specific applications for in-depth analysis as well as provide improved functionality and compatibility for broader use and easier data access and management.
Data management and a new level of intelligence
As MS instruments, and the data they generate, continue to progress, software must evolve concurrently, developing data collection methods in a more intelligent manner. “Many software applications today have intelligence built in, but not yet at the level of AI whereby the instrument is capable of learning from previous runs and determining which data matters and which does not. For the most part, that decision is made by the user after the data has been acquired,” explains David J. Edwards, Ph.D., senior director of mass spectrometry marketing in the life sciences and applied markets group at Agilent Technologies. Edwards also notes that this can create inefficiencies. While an instrument takes time to collect data, time to results is further extended for manual data processing and interpretation.
Many software applications today have intelligence built in…
Beyond how customers manage and use their data, companies like Agilent are also considering regulatory requirements. Building intelligent features into software that supports specific regulations and standards can help labs maintain compliance. “Some customers are required to store their data for 65 years, which is a tremendous burden for any company. While the data may be stored in the cloud, a potential challenge is reading or processing that data 20 years on, when the computer operating system (OS) may no longer support the original software. Ideally, data should be stored in an agnostic manner to the OS and the program being used to process it,” adds Edwards. To address this, Agilent’s OpenLab CDS ChemStation Edition now supports the new Allotrope Data Format (ADF). The ADF file format standardizes the collection, exchange, and storage of analytical data captured in MS laboratory workflows, enabling labs to transfer and share data across platforms.
“Agilent is constantly seeking ways to improve the customer experience, developing tools and services that optimize lab efficiencies,” says Edwards. In addition to OpenLab CDS, which is part of a comprehensive software suite that manages MS data and provides access to an open system architecture, another offering is Agilent’s web-based platform, iLab, for streamlined lab management. iLab Operations Software is designed to support operations for centralized labs and shared research resources. New and intelligent data-management software has enabled MS labs to work efficiently with larger data sets generated from more and better instruments.
Networking and the cloud
With massive amounts of data in hand, sifting through it is no trivial task. “MS labs need software with significant processing power and very fast data access to work with large data files. While computing networks that connect files and processes are more widespread in other areas, working with such large data sets across a network has, until recently, not been a viable option for MS studies,” explains Darren Barrington-Light, senior manager of product marketing for the chromatography and mass spectrometry software group at Thermo Fisher Scientific.
A networked chromatography data system (CDS), like the Thermo Scientific™ Chromeleon™ CDS, provides the possibility to control MS instruments and query, compare, and trend large volumes of MS data held in an optionally cloud-based central repository. Including a CDS and a laboratory information management system (LIMS) in a fully integrated data-management solution can securely capture, store, and archive MS data for present and future use. “Enhanced systems are able to take advantage of cloud services, enabling access to more data as well as delivering improved sharing and archiving capabilities,” says Barrington-Light.
The Thermo Fisher Platform for Science is one of a new breed of software platforms that bring the benefits of networking and the cloud to MS-based research and can expand the usability of large data files, allowing movement and sharing of data for further analysis or interpretation. More importantly, MS labs can make use of additional software on the network for application-centric analysis such as with Thermo Scientific™ Compound Discoverer™ for untargeted stable isotope label flux analysis, or the mzLogic algorithm that ranks chemical database hits.
Opening the door to any application
Because the field of mass spectrometry is so broad and covers a multitude of applications, there is no single software package that does everything. While this raises the complexity in most MS labs, it has given researchers the opportunity to develop innovative software to deal with new problems. “Competition between vendors and third-party suppliers has led software development. We’ve found that collaboration with third-party vendors has made it easier to develop new data interpretation methods and for our customers to choose solutions that are best for their needs,” explains Robert B. Cody, Ph.D., product manager in mass spectrometry at JEOL USA.
Any area that uses MS has seen software developments that enable new research. “One of the earliest examples is biological mass spectrometry, followed by proteomics and metabolomics, where developments are constantly occurring,” comments Cody. JEOL recently introduced MS Fine Analysis that automates reporting for GC/MS analysis, combining the information from electron ionization mass spectra with soft ionization mass spectra for the same compounds.
Biocompare’s Mass Spec Search Tool
Find, compare and review mass spec
tools from different suppliers Search
Chemometrics and other newer fields are more recently benefitting from MS and software innovations, like JEOL’s Mass Mountaineer used for mass spectral interpretation and report generation, that have attained higher resolution and increased amounts of data than previous approaches. Cody notes that petroleum mass spectrometry, a data-intensive area, uses tools such as Kendrick mass defect graphs that are now being applied to polymer analysis, environmental studies, and more.
Another area where software is critical is multidimensional chromatography combined with mass spectrometry (GCxGC/MS). Combining the separating power of GCxGC with high-resolution MS provides a great deal of information. JEOL collaborated with software developers and environmental researchers on the application of Kendrick mass defect analysis to GCxGC/MS data to trace contaminants in the dust from an electronics recycling facility for their successful detection and identification.
Universal software
When choosing MS instruments and software capabilities, consider that each vendor has its own software, where acquisition software is locked to a platform. However, given the variety and volume of assays performed, analytical labs generally have multiple brands and instruments. With different vendor algorithms for each instrument, the same sample run on two different machines can give drastically different results. “Third-party software can be beneficial in these cases, on the backend where data gets processed, so all data from each instrument gets processed in the same way. One platform that can pull in data from any instrument, store data and metadata, and process structures, peak areas, and identifications in a single large data repository instead of multiple disparate data sets can simplify collection and processing,” says Richard Lee, solution manager at ACD/Labs.
ACD/Labs made a switch in focus to a solution-based approach with their vendor-agnostic Spectrus platform (a processor, database, and analytical tool) a few years ago. The first of these solutions is MetaSense, which can process xenobiotic metabolism studies with integration of metabolite prediction. This approach allows the development of a base platform to manage unified analytical data from multiple techniques and instruments on top of which different functionalities can be added depending on research applications and goals.
A recently enhanced data analysis tool for use on the Spectrus platform is their deconvolution algorithm for co-eluting peaks and noisy baselines for LC/GC/MS data sets. As sample analysis becomes more complex, co-elution of components is nearly unavoidable. This algorithm enables chromatographic deconvolution where overlapping peaks are analyzed to pull out compounds of interest so manual adjustments that distort the data are prevented. An extension of the deconvolution algorithm automatically searches spectral databases to aid in compound identification. This new database query feature presents an extensive, unbiased, and relevant list of structures, easing resource strain for deformulation of complex MS samples.
Innovations in MS imaging
As a powerful MS tool for visualizing the spatial distribution of molecules, mass spectrometry imaging (MSI) has enabled higher resolution investigations into tissue and other biological samples for health state and disease characterization. With the ability to detect an array of ions in one image, researchers can look for specific ions of interest and how they are distributed throughout a sample.
However, Dennis Trede, director of SCiLS at Bruker, notes, “Given that MS imaging is data-intensive, severe bottlenecks arise in data screening and analysis, requiring the comparison of millions of spectra from a single data set, sorting through meta-information, and data sharing for interdisciplinary studies.” These tasks can be difficult with manual analysis and site-specific licenses. Using specialized cloud-based software like Bruker’s SCiLS for more automated analysis and easy file sharing overcomes these challenges for achievable results across discovery, absolute quantitation, and 3D imaging applications.
In discovery studies, Trede offers that MSI and SCiLS enable the use of spectra to distinguish changes in diseased tissue when compared to healthy tissue and find markers with spatial similarity to regions of interest. Louise Carlred and colleagues from the Institute of Neuroscience and Physiology at the University of Gothenburg used MSI to investigate the pathological mechanisms underlying Alzheimer's disease, specifically the factors that promote the accumulation and aggregation of amyloid‐β (Aβ) peptides into extracellular plaques. Using Bruker’s SCiLS software, the group was able to elucidate the spatial distribution patterns of Aβ deposition in transgenic mouse brain tissue and the plaque‐associated chemical microenvironment.
The volume and complexity of data being generated by high-resolution mass spectrometers has created a push for new software tools and new databases that comprehensively support and simplify data processing and interpretation across multiple instruments and applications. Here, we have given several directions software development has been taken in the rapidly evolving field of mass spectrometry.