The End Game has Changed

By Sheila Colby, Ph.D. on May 16, 2011
Sr. Scientific Product Marketing Manager, IPA

When I was first introduced to pathway analysis, more than ten years ago, the end game was a living-color understanding of a biological pathway itself. Who’s on first base, second, and third?  What is the nature of their relationships? What happens when this or that molecule is perturbed?

Over the years, much has been learned. Hundreds of important pathways are well characterized now, and a great deal is known about the molecular relationships in them. The scientific discoveries that underpin these pathways are tucked away in full-text literature and in many different public databases, such as KEGG. Yet a lion’s share of important biological findings is housed in one integrated and centralized location, the Ingenuity Knowledge Base.

Unlike specialized biological databases, the Ingenuity Knowledge Base is comprehensive, crossing many disciples (i.e., biochemistry, genetics, and molecular biology); molecule types, and instrument platforms; is intensively scrutinized for quality; includes findings from the original literature, leading public and 3rd party databases; and is captured in an exceptionally granular ontology. Here researchers can tap into important findings, all in one place, at any time.

The real challenge now is navigating quickly in to answer, “which bits, buried deep within this enormous mountain of biological and drug information, pertain to my experimental question?” Then, “which bits help me make the most biologically informative interpretation of my experimental results”? Given the daunting task of tackling complex diseases, with inherently insane levels of complexity, the end game has now changed.

It’s about efficient and biologically meaningful interpretation of the complex experimental data generated by contemporary HTP instrument platforms.  Due to these advanced tools, questions can be much more global and personal at the same time. For example, if an individual has a stroke and then later Alzheimer’s are these “isolated incidents” or are they connected, and if so, how? Answering these larger questions means integrative biological approaches, advanced computational analytics, and superior visualization tools up to the task of effective global navigation of these complex systems.

It also highlights the need for ever more advanced tools that make it possible to intersect genetics (phenotype-genotype focused), gene expression, epigenetic analysis (environmental influences), and other disciplines. New technologies such as NGS can help flesh out the really big picture in ultra high definition. “Are specific disease connections, cascades, or subtypes due to a specific pattern of alleles of several genes? Splice variants of mRNA? Post-translational modifications, epigenetics modifications, genes up or downstream? Some unfortunate combination of the above? Or something else, yet to be discovered?”

While the advent of instruments for high-resolution biology holds great promise, they also transform existing informatics pain into acute pain. Thus, what we have in the past called “pathway analysis” software has become the de facto “Google Earth” application for navigating complex biology. The new end game for IPA is to help scientists quickly get to the information that is the most relevant to their experiments or explore the details of related biological models. The interactive nature of IPA lets a scientist zoom into something interesting, then zoom back out once enough information has been gathered. Visual, interactive navigation has become the proven way to meaningfully interpret biological data.

This shift from “pathway analysis” to pathways as an integrative biology navigation map fundamentally empowers researchers to efficiently navigate and visualize experimental results (in a very meaningful way) within a complex landscape of important findings about the complex system du jour. IPA does far more than allow a researcher to analyze a pathway, while of course one can still do that. Ingenuity is committed to helping scientists best take advantage the fabulous new high-resolution instruments by providing efficient tools for biological interpretation that leverage the vast detail and exceptional accuracy that they provide.

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