Although electronic lab notebooks (ELNs) have been steadily replacing paper lab notebooks for almost a decade, their acceptance in chemistry-based disciplines has far outweighed their use in biological research. A basic ELN is a device or software that is able to store various laboratory data types, from calculations to notes prepared by researchers. The data can then be easily recalled, manipulated, searched for and shared. One of the most important functions of an ELN is to provide patent protection, allowing the documents it holds to be electronically signed and witnessed, while being secure from tampering or theft. Over time, ELNs have evolved into multifaceted devices with capabilities that run the gamut from being able to read and manipulate image data directly from an instrument to having the ability to analyze data. As ELNs continue to evolve, companies such as IDBS, Symyx Technologies and Rescentris are working to optimize ELNs to fit the biological research landscape.

In creating an ELN for biological research, the difference between biological and chemical research must be taken into account. First of all, in the field of biology, experimental parameters are more frequently modified. Biological experiments involve multiple researchers and tend to be more time intensive, generate more data and involve more different types of data. Companies providing ELNs for biology must strike a balance between addressing the specific application needs of biologists and providing a flexible platform for the control and integration of structured and unstructured data. Symyx, IDBS and Rescentris have tackled the problem of providing ELNs to the biological research market and maintaining this balance, but each in a different manner.

Symyx’s newest ELN, the Symyx Notebook, is a multidisciplinary ELN that comes with software customization tools, providing flexibility to all researchers involved in drug development, rather than only focusing on biologists. Until recently, Symyx has offered ELNs primarily for chemistry applications. The company’s focus on the pharmaceutical market and the need for total data integration has shaped its multidisciplinary approach. According to John McCarthy, vice president of Applications Product Management, Symyx is “focused on delivering a notebook for the enterprise that is not a notebook just for a medicinal chemist or a biologist, but one that recognizes that there are many scientific disciplines and domains to get a drug to market. These different disciplines and domains need to be able to work together to exchange information and to progress their research and release of drugs more quickly.” The Symyx Notebook, introduced in April, is designed for use in both biological research and analytical chemistry. The Notebook comes with a software development kit to allow for adaptable functionality and can be integrated with numerous third-party applications for data management and analysis.

Mr. McCarthy explained how Symyx’s multidisciplinary approach emphasizes data integration. “There’s so much that takes place within biology and pharmaceuticals. It is unstructured. It’s not run by a robot. It has to do with animals being tested, samples being weighed out or pipetted by hand,” he said. “Our view is to allow HTS [high-throughput screening] and robot-based assays to continue on with what data management systems they have in place today, but also support those unstructured experiments and bring them into the same platform so, [for example], you can get a more holistic view of the initial screening through the DMPK toxicity tests that have been done.” Integrating data also requires working with multiple programs. “It’s also about integrating the other applications that a biologist uses such as Excel, GraphPad, Prism, etc.” Symyx’s bioinformatics experience, according to Mr. McCarthy, gives the company insight into the need for the right balance in handling structured and unstructured data. “Our customers are trying to utilize LIMS and [Symyx’s] Assay Explorer like they are ELNs, and now that those groups know what it’s like to manage their data electronically, they’re putting the rest of the ELN around it: the document approval, workflows and e-signature approval that ELNs provide.”

Symyx has also positioned itself in the ELN market through the acquisitions of MDL (see IBO 8/15/07), a company specializing in chemical and biological informatics, and Integrity Biosolution (see IBO 8/15/08), a research company specializing in large molecule studies. The acquisitions addressed two main problems when introducing ELNs to the biological research sector: application development and laboratory integration. “To date, most of our notebooks are focused on process chemistry and medicinal chemistry for small molecule research, but, of course, the pharma world is moving very rapidly into large molecules and biologics,” explained Mr. McCarthy. “We now have added scientific know-how with the Integrity Biosolution acquisition for bioformulations, and what it means to do high-throughput research around bioformulations and biomolecules,” he said. The acquisition of MDL brought a customer base and pharmaceutical industry knowledge. In addition, it added MDL content directly to the Symyx ELN and also bolstered the company’s customer support expertise in biology and DMPK work. “We [now] have people in the field who can speak directly to a biologist, who have been through some of the [data] change management aspects that I spoke of earlier,” said Mr. McCarthy. “So it’s really the know-how that those groups have brought to Symyx that have made it easier to move our customers from a paper notebook to an ELN.”

IDBS’s approach to biology ELNs is more direct than that of Symyx. The company offers an ELN specifically for biology, the BioBook, and provides application extensions for its multidiscipline ELN, the E-WorkBook, which can tailor the E-WorkBook towards biology-specific applications. All of IDBS’s ELNs are upgradeable with application extensions. The soon-to-be-released Suite 8.0 will add further biological data management capabilities to the multidisciplined E-WorkBook. Current extensions to the E-WorkBook also include applications for statistical calculations, charting and LIMS-type functions.

However, IDBS’s ELNs for biology and biology extensions do not unnecessarily restrict how the user is able to handle data. The basic building blocks of biological ELNs, according to Glyn Williams, vice president of Marketing and Product Management at IDBS, is that biological ELNs, more so than chemistry ELNs, must integrate varied data and also be able to work with unstructured data: “Integration is a big challenge in biology because you need to integrate with a lot of different systems—because they have what’s called ‘parts of structured data,’ such as Excel sheets or graphs,” he explained. “But then you also have what we call ‘unstructured data,’ which would be photographs of gels and microscope pictures. Increasingly, there’s a lot more image-based analysis. So now you have to bring the structured and unstructured data together. The actual framework of an ELN is very well suited to this.”

The periodical release of extension suites is one way that IDBS provides researchers a way to customize their ELNs for specialized applications. According to Mr. Williams, the company developed a modular approach to the ELN market so as to not burden specific labs with unnecessary features. “We basically have this basic ELN backbone and then we have extensions. For example, one is for complex biology, because biology covers a lot of different things, some things are generic and can be managed by the E-WorkBook. In a lot of cases, they want to go to a lower level, like capture [data] from instruments or maybe do statistics.” Such flexibility allows for many choices. “For example, in pharmacology, where you need to do randomization, some need to see the randomization; others don’t, they can just see the data blind,” he stated. IDBS provides ELN extensions for users to view data, eliminating the need for applications to be used from multiple sources and giving the user gains in productivity, while letting researchers decide what applications they need.

Because the goal of a biological experiment is more undefined than a chemistry experiment, data management for biology ELNs requires dynamic and sometimes sector-specific data-collection techniques. “Within biology, experiments tend to be team-based longer experiments, and the end-point is not something like a melting point or a solubility, or something very defined. It can often be a report that will encompass many documents being brought together, or many spreadsheets being collected,” said Mr. Williams. To adapt to the dynamic group environment, the BioBook’s analysis, dosing-regimes, observations and treatment groups can be produced and changed during an ongoing experiment, with calculations, analysis and reports automatically updated. The BioBook currently has extensions for pharmacology and toxicology. Future extensions include genomics, cell biology and proteomics. A new version of the BioBook will be released in the middle of 2009 and it will also be upgraded with a new extension release this December.

Like IDBS’s BioBook, Rescentris’s CERF ELN directly addresses the biological research field, but unlike IDBS, the company embraces the diversity of biology but does not offer specific application extensions. In fact, CERF’s software-development format and ontological foundation keeps the ELN from being too tied to any specific set of biological applications. “It is a client-server application, a full Java application built on semantic technologies. It is the only semantic technology built on ontologies. It works on Macs and PCs or any platform,” said Rescentris CEO Adel Mikhail. He stressed that it is this flexibility that is the CERF’s draw. “The product can be extended by the client. Much of the business logic can be done by the actual user. We don’t hold them hostage to modifying the product.”

In addition to the implementation of a more unstructured data management system, Rescentris’s approach uses inbuilt biology ontologies­—that is, a standard of relationships and definitions between terms and concepts within biology—to create a structured environment for biological data. Mr. Mikhail believes that the two keys to approaching the biological research sector are dynamic data management and a strong ontological backbone. “Chemistry has 400 years of nomenclature and standardization, so it is very easy to build a software package that understands that. In biology, there are 14 or 18 different spellings of the word ‘protein,’ so it is a much more free-flowing discipline, so that requires a different ability for both structured and free-flowing entries of information.” The development of ontologies for biology facilitates consistent searches and makes sharing between researchers and across research fields easier. “[Our system] can understand that the cerebellum is part of the brain, so when you search for ‘brain’ you can find ‘cerebellum’ and vice versa. It builds these ontology-based semantics so you could have better searching,” he explained.

Because the market for ELNs in biological research is relatively new, Rescentris’s user-based software development is still in its early stages. According to Mr. Mikhail, more time is needed for users in biological fields to adopt ELNs. Researchers in more structured research areas, such as high-throughput screening, have been the early adopters. The company believes that over time, as early-adopters begin to develop more sophisticated software for less regimented applications, Rescentris’s entire ELN user-base in biological research will have more options. “Our users are already building modules and plug-ins for the product. Our hope one day is to be able to share these modules,” he stated.