Keeping Track

There comes a point in life sciences research when spreadsheets just don't cut it anymore. It happened two years ago at the Nord-Trøndelag Health Study, a 25-year-old family and personal database of approximately 110,000 people in Norway's Nord-Trøndelag County. The project, a resource for epidemiological, clinical, and preventative medical research known as HUNT, launched its third phase, which boosted its patient population by more than 30% and tipped it into information overload.

"HUNT 1 and HUNT 2 already created a lot of data, and at some point it became very complicated and difficult to work with," says Thor Gunnar Steinsli, an information technology (IT) manager for the project, which is run by the Norwegian University of Science & Technology, in Trondheim. The laboratory had been tracking blood and tissue samples using basic computer charting tools such as Microsoft Excel, Steinsli says, "but with three studies going on, this system was not capable enough. Not by far." HUNT, he says, needed a LIMS—a laboratory information management system.

LIMS denotes a diverse class of software used in labs to collect data on experiments and track samples. Some LIMS products provide a level of workflow automation as well as invoice and instrument monitoring. Overall, LIMS systems enforce standard laboratory practices by creating a central repository for samples and data. HUNT purchased a Nautilus LIMS system from Thermo Fisher Scientific to manage its collection and tracking of 800 to 1,000 medical samples a day, five days a week.

Steinsli explains, however, that a LIMS system needs to work in conjunction with existing software and automation. The Nautilus system needed to integrate with an RTS Assay Station fractionation instrument and a Tecan plate scanner. It also needed to be linked to an Oracle database for lab sample data and a separate in-house database for patient information.

The IT and instrumentation landscape at HUNT is not atypical in the life sciences. Research IT has traditionally consisted of a wide range of homegrown or jury-rigged software programs. But in recent years, labs have started adopting more comprehensive commercial products such as LIMS. This shift has been prompted in part by genomics-based research, which has exponentially increased the volume of data that need to be collected, managed, and analyzed.

The advent of translational research—the practice of linking drug discovery to human clinical trials with two-way data communication—has also sent research organizations in search of software to facilitate the link. Software suppliers, in turn, are expanding the capabilities of their core products and forming partnerships with other suppliers in order to cover everything from raw data collection to in-depth analysis.

According to Ruchi Mallya, a pharmaceutical technology analyst with the market research firm Datamonitor, the trend in the life sciences is toward software integration.

Building a single IT network, however, is no easy task, according to Mallya. "Because of the changes under way in life sciences, the IT industry serving the sector isn't fully developed yet," she says. "Much of what is being done in the laboratory is routine, however, and software vendors are popping up left and right. Some consolidation is taking place, some vendors are trying to make it on their own, and some are partnering with other vendors. Others are developing user-specific systems and then commercializing them."

Laboratory research IT can be viewed as a three-tiered pyramid with an information gathering and process management layer at the bottom, an executive decision-making tier at the top, and a more nebulous "middle management" layer in between. It is at that middle level that information tends to be stored and analyzed and accessed from both the top and the bottom. But it is at the bottom level—the LIMS level—that actual research takes place.

Researchers' needs and software vendors' offerings vary widely at the bottom of the pyramid. Thermo Fisher, one of the largest suppliers, has several LIMS systems for both the chemical and life sciences markets. They include Sample Manager, a generic LIMS; and Watson, Darwin, and Nautilus, products tailored to more specific aspects of life sciences research.

According to Seamus Mac Conaonaigh, Thermo Fisher's director of technology for informatics, the trend in software development has been toward systems that allow users in specific research sectors to easily access, format, and route data. "The reason this is important is that the hardware and instrumentation in labs is generating absolutely colossal amounts of data," he says. "It is not enough just to get it. You need a way to make sense of it."

The standard practice of relying on Internet services to route data from the LIMS is inadequate, Mac Conaonaigh maintains. "That still places the onus on the customer to figure out how that integration is supposed to happen," he says. "We are certainly providing them with the tools to get at the data, but what to do with it and the actual business of writing the software to get the data out and put it into another system is still something they have to do if vendors only provide them with Web services."

To that end, Mac Conaonaigh says Thermo Fisher consults with customers on ways of aggregating data through commercial portals like Microsoft's SharePoint, which are becoming ubiquitous in the life sciences and which many specialized software providers are promoting as a means of system integration (C&EN, May 26, page 13). Thermo Fisher will also introduce a version of its LIMS software that is compatible with Microsoft's BizTalk server, a technology for connecting disparate business IT networks.

According to Mac Conaonaigh, the big challenge in software system design is gauging scale and scope. Laboratories and clinics traditionally have not shared data, he adds. And just getting big drug companies and research institutes to think about new approaches to configuring IT can be daunting, particularly if the Food & Drug Administration regulates them. "This is a very conservative industry," Mac Conaonaigh says.

Like it or not, however, the life sciences sector is going through big changes, especially in the laboratory. Ron S. Kasner, vice president for corporate development with Labvantage, another major LIMS supplier, says managers at drug companies and research institutes recognize a need to implement operational intelligence networks similar to the business intelligence networks launched in manufacturing and financial industries in the 1990s. The key, Kasner says, is an integration of data gathering and analysis.

Labvantage has expanded its Sapphire LIMS in recent years to accommodate new trends in research. "We've added biorepository management," Kasner says. "We have advanced storage and logistics for tracking and package handling, stability and reagent management, and other R&D applications." Such features are offered as part of a single IT platform that can be configured to afford flexibility at individual laboratories but also promote standard practices at global research organizations.

The company's most recent LIMS adaptation is software for accessing, reporting, and analyzing disparate data. For this, Labvantage has formed a partnership with InforSense, a supplier of data integration and predictive analysis software. Under the agreement, Labvantage will market InforSense's software along with its Sapphire LIMS.

Simon Beaulah, senior marketing manager for InforSense, sees advantages to both laboratory managers and bench scientists in combining LIMS and data analysis software. "We provide visualization tools through the Web," he says. "You can think of it as scientific business intelligence. It is a matter of getting the right data to the scientist so that the scientist can make the right decision." Translational research is a major impetus for adding an analysis dimension to standard benchtop computing, according to Beaulah.

James DeGreef, vice president of market strategy with LIMS provider GenoLogics, says his firm is working on integrating its LIMS with InforSense software. "LIMS and analytics working together is a trend now," DeGreef says. "It's a natural fit." Researchers are interested in integrating these functions to advance proteomics and genomics research, which are key practices among GenoLogics' target customers.

Like Labvantage, GenoLogics adds features to its LIMS software on a regular basis. But partnership with other software suppliers has long been a route to linking with completely different kinds of software and automation. "A lot of our work is done with instrumentation providers," DeGreef says, citing a partnership with Illumina, a gene sequencing and genotyping systems supplier.

According to DeGreef, the LIMS market is trending away from generic software to products targeted at specific areas of research. GenoLogics, which has always targeted the life sciences, offers a basic system called Omix, as well as a specialized product for genomics called Geneus and one for proteomics called Proteus.

Given the need for software customization and the availability of Web-based tools to connect software, Biomatrica, a LIMS supplier launched five years ago, sells its software as a series of modular applications. "We are seeing a trend away from big, monolithic LIMS systems that try to capture all the data at one time," Brian Baumann, director of software products, says. Although large-scale systems might work well in biobanking applications, Baumann says, drug and biotech research can be handled more efficiently by linking modular software components at the bench to a central database.

Baumann adds that new product development at Biomatrica also focuses on ease of use—developing software that can be maintained by the researcher. "In a lot of big pharma and biotechnology companies, IT departments don't support scientific software," he says. "They deal more with IT infrastructure. LIMS needs to be made more intuitive to the user." And LIMS must be easily integrated with other laboratory software and automation, extending the modular approach into a multivendor IT landscape.

Some software developers have launched new products operating at the middle level of the lab IT pyramid that are specifically designed to link research software and databases. BioFortis, for example, has introduced software called LabMatrix that vets data collected by LIMS at the laboratory level and routes it where it is needed.

"LIMS are involved in gene expression, imaging, and converting information into numbers, but not every number needs to be carried up the pyramid," Jian Wang, chief executive officer of BioFortis, says. "All that matters is the numbers that change in a meaningful way. The rest is just noise. You need a layer of abstraction from the raw information managed by the LIMS, a level at which you can manage multiple streams of data."

According to Wang, BioFortis is exploring partnerships with other software firms. "One of our clients wants us to pair up with its LIMS vendor," he says. Wang emphasizes that there is still a high level of software customization necessary for laboratory IT. "LIMS is still a hodgepodge, especially in academic labs," Wang says. "It's even messy at pharmaceutical companies that operate in a regulated environment."

Wang and other vendors agree, however, that the life sciences industry is generally cleaning up the mess. Frank Brown, director of business development for Accelrys, a supplier of modeling, simulation, and informatics products for chemistry and life sciences research, sees a laboratory IT systems convergence that mirrors the convergence occurring among research departments under the rubric of translational research.

"There is a cultural change under way at pharmaceutical companies," Brown says. "They realize the handwriting is on the wall. A lot of small molecules are coming off patent, and they need new ways to do business, new ways to develop compounds that don't have huge blockbuster potential but can still be developed efficiently for targeted subgroups of the population."

But the change in operating model will precede IT systems realignment, Brown says. "There needs to be a different business and operations model in which all levels of the company are working together, as opposed to a linear or serial process," he says. "A dramatic flattening of the entire organizational structure must be in place before the software is in place."

Hai Hu, director of bioinformatics at Windber Research Institute, in Windber, Pa., attests to the impact translational research has had on software development. Windber, he says, began installing an InforSense system in 2005 to supplement its database with analytical capability. More recently, the firm has begun replacing an old LIMS system—Windber had been a pioneer user of software from Cimarron Software—with a GenoLogics system to work in conjunction with InforSense for data tracking and analysis.

The project was prompted by researcher demand for data management in translational research, Hu says. Linking LIMS to the InforSense software is important, he says, because of the volume of data moving between the clinic and genomics and proteomics researchers.

According to Hu, Windber is also harnessing the ability of combined LIMS and analysis software to vet databases for pertinent information.

The use of LIMS varies widely from one research organization to the next, however. Pfizer last month signed a global LIMS supply agreement with GenoLogics. According to Giles Day, head of informatics for the drug firm's newly launched Biotherapeutics & Bioinnovation Center, the incentive for the project is the drastic increase in data from genomics- and proteomics-based research. Software is being installed first at the company's Research Technology Center, in Cambridge, Mass., and at its Pfizer Global Research & Development lab, in Sandwich, England.

"Basically it replaces ad hoc site by site workflow software," Day says. "We had a desperate need for a way to manage laboratory information from omics research. But across all of Pfizer there is a similar picture."

At the Virginia Bioinformatics Institute in Blacksburg—an eight-year-old research consortium—software was needed to support a diverse array of laboratory investigations in computational science, biology, systems biology, and infectious diseases. According to Michael Czar, VBI's senior program manager for synthetic biology, the institute is using Biomatrica's SampleWare LIMS to track large numbers of oligonucleotides, plasmids, and DNA constructs in laboratories and to track bacterial cell lines.

The LIMS system replaced Excel spreadsheets and a Wiki-based system designed in-house, he says.

Collaboration is also an incentive for IT integration. The Multiple Myeloma Research Consortium (MMRC), a project involving 15 research institutes, including Dana Farber and the Mayo Clinic, installed a Labvantage LIMS in 2004 to manage a shared tissue bank in Scottsdale, Ariz. The bank currently holds 1,800 myeloma tumor samples and 1,400 matched peripheral blood samples. The group has opened 15 clinical trials since 2005 and is on track to start seven in the coming year, according to Bunmi Mfuko, tissue bank coordinator. MMRC operates a public portal hosted at the Broad Institute, which allows general access to researchers.

MMRC is currently investigating an extension of its data capture and tracking LIMS to support investigator-initiated clinical trials, she adds.

Laboratory software remains a mixed bag of technologies serving a wide range of needs—needs that vary among researchers within the same institution. While Web services and products like SharePoint facilitate fairly broad connections between software products, there are no true "out of the box" solutions in the life sciences sector.

"It's never as simple as deploying technology that is already used in other industries," Thermo Fisher's Mac Conaonaigh says. "It comes down to domain expertise. In addition to people like us who know the technology, you need to have people who know the business who can make the system work."

And user resistance to IT—be it the institution or the individual researcher—can never be underestimated in the life sciences. Nor can privacy issues and competitive concerns over proprietary data.

MMRC's Mfuko notes that although the consortium shares a LIMS for managing its common tissue bank, its members balked at installing the InforSense workflow analysis software, which would allow consortium members open access to each other's databases and would also allow access to proprietary data via the public portal. The result is that researchers cannot access patient information from individual databases through the LIMS system. "For that," Mfuko says, "we rely on Excel spreadsheets."