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Watson for Drug Discovery

More than nearly any other field of study, science is cumulative: each new breakthrough is built upon the understanding established by those that came before it, and therefore has value not only in itself and its applications, but also as an investment in the foundation from which future findings will inevitably spawn. But before they even set foot in the lab, this fractal nature of discovery poses a paradox to biologists searching for cures to genetic diseases like cancer. Their roles require them to have the most recent relevant knowledge available; without it they risk investing millions of dollars and man-hours in an uncertain direction. And in a world where less than 1 in 5,000 explored drugs make it to market, and those that do take over a decade to get there,* researchers cannot afford to set sail in the wrong direction. The irony lies in the fact that to keep up in the rapidly changing realm of biochemistry, researchers would have to spend more time reading than there are hours in the day—the very discoveries they depend on drown them. Fortunately, with the arrival of cognitive computing, the sheer quantity of data is the opposite of a problem: it is an opportunity. Watson for Drug Discovery uses machine learning to parse data sources, surfacing relationships between genes, drugs, and diseases with the goal of guiding researchers in selecting potential drug candidates to explore and invest in.

*As documented in MedicineNet’s Drug Approvals—From Invention to Market ... A 12-Year Trip article.

Project pretext: Professional
Assignment: Design a data visualization to increase user understanding and productivity
Timeframe: 6 weeks
Role: Lead data visualization designer
Additional team members: 1 UX designer part-time, 1 developer part-time

Opportunities

Process

Opening the wet lab to a long list of genes suspected to be connected to a disease is expensive. One way to filter down the collection is to compare it to known genes—those with relationships to the disease that the research team is already aware of. Predictive Analytics (PA) is one of several tools available within the Watson for Drug Discovery (WDD) offering, and it aims to provide just that capability by searching for similarities between the way candidate and known entities* appear in publications. The way its results and the evidence that back them were originally conveyed, however, often left users more baffled about what to do next than they were before they opened the app. I was brought onto the WDD team to redesign the way this data and its insights were visually communicated.

*When it concerns Watson, an entity refers to a single biological concept consisting of various synonyms in literature. Aspirin and acetylsalicylic acid both represent the same molecule, so they are synonyms of the same entity. The cognitive services that make up Watson look only at entities in order to make accurate but otherwise easily missed connections. The algorithms used for this project recognize entities resolved from synonyms that refer to a gene, a chemical, or a disease.

The data science behind PA is complex; it goes far beyond simply surfacing sources wherein searched entities co-occur. Before I could design a way to better present the results of the data model to users, I needed to understand it myself.

A sketch I made as shorthand for myself while talking to our data scientists, featuring documents, terms, and input entities, and how these fit together to form the data model behind Predictive Analytics.

I met with the data scientists who’d created PA’s data model and its original visualizations. Once I had an abstract understanding of the steps that happen behind the screen, I came up with a simple scenario and sketched out conceptual illustrations. This helped me gain a more tangible grasp on the way results were generated.

And that was about as far as I got with my understanding of Predictive Analytics’ as-is state. Its tree visualization felt suspiciously arbitrary on several levels. It was built on the idea that similar entities would accumulate near each other—but nodes within each layer were stretched so far apart to accommodate their own children nodes that physical proximity was not a valid metric of measurement at all.

A massive tree diagram contains all input entities, forcing early-placed nodes apart from one another to accommodate their children nodes.
The original visualization was a branching tree, the primary node of which represents the entity whose found terms and ratios are most similar to those of the known inputs. From there, its children nodes consist of the genes—candidate or known—most similar to the the primary node specifically. Subsequent nodes follow, chosen exclusively for their similarities to the previous layer’s nodes. It seemed like a stretch to claim that this format helped researchers narrow down which genes to study in more depth.

It came as no surprise that the tree routinely intimidated and perplexed users. Its focus on hierarchy seemed to them to suggest natural order. Nature branches as it evolves, conceptually leaving tree-like fractals of change in its wake. From taxonomies of living organisms to the structural similarities between chemical molecules, humans organize newfound knowledge of the natural world into nested sub-divisions. To a biologist, a branching framework intuitively suggested results of empirical origin.

“Given that it [the tree] only has these two-way splits at every node leaves open the possibility that things that wind up far apart on this tree are actually not so dissimilar, or maybe they have a closer relationship than it would appear … I became really quite confused about how I was to properly interpret the tree and discouraged that I might be missing things.”

—biologist, after having had access to Predictive Analytics in its original form for 30 days

Furthermore, a hierarchy fundamentally failed to communicate the data accurately. It forced the results into a veritable corporate reporting structure, whereas the actual data model used to find similarity treated all inputs equally throughout the process, comparing them round-robin style. A network or force diagram would more accurately reflect these relationships in the data, while allowing the user to explore their inputs’ relative similarities. A quantitative method like a list could be used to rank the candidates genes based on their similarities to the known genes, and would more directly inform users as to which entities might be worth pursuing further.

A force diagram features all inputs, both candidate and known, clustered according to their attractive forces, which are informed by their relative similarities.
I worked with a developer to prototype a force diagram, using real data. Attractive forces are programmed into each entity’s node, based on their similarities to every single other entity. The nodes, with their physics-mimicking forces, jostle and sort themselves out accordingly. In order for every node to be in the perfect position as demanded by its similarity measurements, the visualization would have to exist in a world with n-1 dimensions (where n = number of nodes). That means that this design functions as a flattened approximation, potentially useful for our users as an exploratory starting point.

Our users might need to assess several facets of the data simultaneously, to accurately compare and gain context. My favorite part of designing a data visualization is working out which “visual variables” (as I affectionately and alliteratively call them) to employ together, in order to provide these layers of meaning to the user. Sketching allowed me to quickly explore all sorts of shapes, colors, and other visual aspects that could be layered onto the nodes, thereby conveying multiple attributes of the data simultaneously.

Sixteen sketches exploring all sorts of node embodiments.
The user would need to quickly differentiate their known entities apart from their candidate entities, to easily identify similarity patterns between them. They might also want to know at a glimpse which candidates ranked highly in the list, or if a node represented a gene, a drug, or a disease. These attributes of the data could be represented at once through the layering of "visual variables".

Some aspects of the data could not be encoded visually, such as the evidence specifically supporting an entity’s particular location in the visualization. In the original design, if users had wanted this information, they would have had to select exactly three entities from the tree. They’d then be greeted by a spinning 3-D cloud of colored pixels symbolizing individual documents that mentioned one of the selected entities. The only way to actually drill into the supporting literature itself was to click on a swirling colored speck at random, which opened the document it represented.

Three circles, each representing a selected entity, are surrounded by a mass of colored pixels representing individual documents.
In addition to being inaccessible to color-blind users, the swirling mass of colored pixels standing in for documents didn’t portray the data model accurately or transparently: no mention was made of the found terms that formed the basis of the similarities between entities.

A far more accurate depiction of the data seemed to be in the form of a word spectrum. Typical word spectrums place two concepts being compared at opposite ends of an x-axis, while terms common to both fall on the spectrum between them, their left-to-right location dictated by their relative association strength to each of the two concepts.

Three differing word spectrum styles: a typical one with two concepts on either end of the x-axis with variously sized terms filling the space between them; another with a similar layout but featuring circles around each word with a bar-chart-like background; and one with a sun ray motif in which stronger terms appear closer to the inside.
I started my endeavor into improving the evidence visualization by researching various takes on the word spectrum concept.

Armed with inspiration from my research about word spectrums, I turned to the drawing board to help me think divergently, exploring every manifestation of the data I could come up with.

Twelve sketches iterating on the concept of a word spectrum, more or less.
My first thought was to increase the number of entities being compared at once, from a pair to a trio, as seen in the top left sketch featuring pie charts, the diameter and breakdown of which represent occurrence. But this concept muddied the true data model upon which the list and force diagram results were built: it did not transparently communicate the fact that each entity was compared to every single other entity at an individual level. Keeping the word spectrum to just a pair of inputs enforced this, so I continued to explore. Another idea I had featured a scrubber that allowed the user to scan resulting terms by their polarity along the x-axis.

I consulted a fellow UX designer for feedback on my sketched ideas to narrow them down for concept testing with users. We built out three of the most promising ideas and asked five WDD users for their thoughts.

The initial pass with users helped us to narrow down our direction further. I wanted to know how the terms would communicate their occurrence strength if we rendered them as bubbles versus simply relying on their font size. I worked with our developer to mockup prototypes connected to real data, which my teammate and I tested with three more WDD users.

Both renderings had strengths and weaknesses, but in ways that complemented each other: it seemed to me that success might be found by combining the distinct outline afforded by the bubbles with the more economical shape of the words.

Outcomes

Predictive Analytics is a tool within the Watson for Drug Discovery offering that analyzes semantic similarities between genes, drugs, and diseases. It outputs a ranked list of inputs to help researchers narrow down long lineups of potential targets and determine which are worthy of further exploration. Additional visualizations allow users to analyze specific similarity relationships as well as the reasoning and evidence backing them.

A list of candidate entities with their relative ranks revealed as a bar chart and the distance network with all inputs, both candidate and known, clustered according to similarity.
The list on the left ranks candidate entities by their similarity to all known entities, the relative strength of which is visualized by horizontal percentage bars. This same similarity measurement for each candidate is surfaced in the distance network: fully saturated red nodes represent entities most like their green counterparts, while nodes with white fills are least alike.

Each node possesses attractive forces correlating to the similarity between it and every other node. The relative strengths of these forces draw some nodes together and distance others, resulting in a landscape that symbolizes the inputs’ collective similarities.

The collection of technology and algorithms that make up “Watson” interpret data differently than humans do; in the case of Predictive Analytics, rather than using empirical evidence, Watson looks for patterns in the way entities appear in literature. The potential value to this approach lies in the idea that the author of a paper or patent may embed biological attributes within the phrases they use to describe entities.

This is a completely different method than most life sciences researchers are accustomed to. Given the historical confusion caused by Predictive Analytics, coupled with its users’ natural inclinations as scientists to question how all things work, I felt it was imperative to educate users upon entry.

Hovering on a node in the distance network reveals the top five inputs most similar to it. Selecting a pair allows the user to dig deeper into the nature of their semantic similarity via a word spectrum.

Words appear along the spectrum’s x-axis according to their relative occurrence in literature with the selected entities, which occupy either end of the x-axis. A term’s height symbolizes its likelihood above mere chance of co-occurring with either entity in the literature, relative to the other terms in the spectrum.

A word spectrum with its various data-communicating dimensions called out.

Patterns formed by the collection of terms in the word spectrum can be significant. A gathering of terms near the center indicates that the selected entities notably overlap in the literature; terms that stick to the fringes suggest less similarity.

Two examples of the Predictive Analytics word spectrum featuring real data: one in which terms gather near the center, and one in which they disperse toward the sides.
The central location of terms associated to the entities PIM1 and PIM3 indicates that the genes share several common words and ratios of occurrence. EPHA3’s and DYRK2’s terms are more clearly clustered into two groups on either end of the spectrum, revealing that the way these genes are written about in literature differs significantly.

A modified butterfly chart accompanies the word spectrum; the user can search for a specific word or word-part and see matches highlighted in both visualizations. Selecting a term from the list or spectrum drills down into the supporting literature.

Although Predictive Analytics follows a vastly different epistemological model than the traditional, empirical approach to drug discovery, the unique perspective it offers has proven to be helpful. Scientists at Baylor used it along with other WDD tools to validate two p53 kinases* in just two weeks, when the industry average is just one per year, globally. Up to this point, only 28 of these specific proteins had been discovered in the past 35 years. Meanwhile, to quote IBM’s 2016 Annual Report, researchers studying amyotrophic lateral sclerosis (ALS) at Barrow Neurological Institute “employed Watson for Drug Discovery to study nearly 1,500 genes in the human genome, and found five that had never before been associated with ALS.”

*According to the IBM Research blog “the p53 protein reacts to the detection of genomic problems by increasing the expression of hundreds of other proteins to try and fix these issues, and can even instruct potentially harmful cells to destroy themselves. It gets these calls-to-arms from another set of proteins that chemically modify p53 in response to particular biological conditions.”

“So, it’s [Predictive Analytics] really been a sort of hypothesis generating tool for us. But, a very useful hypothesis generating tool because it’s led us … in quite reasonable directions.”

—biological researcher, after having used the newly designed Predictive Analytics visualizations for 30 days

As such, Watson for Drug Discovery has been mentioned in a number of news articles and has been the subject of several scientific publications.

Press

Pfizer’s 2016 Annual Report

International Business Times: Here Is IBM’s Blueprint For Winning The AI Race

Information Week: IBM Watson Speeds Drug Research

Scientific publications

Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA‑binding proteins altered in amyotrophic lateral sclerosis

IBM Watson: How Cognitive Computing Can Be Applied to Big Data Challenges in Life Sciences Research

Automated Hypothesis Generation Based on Mining Scientific Literature

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