Thursday, January 9, 2014

BARD - helping you answer Who, What, When, Where, Why and How about BioAssays

A basic framework that many of us were taught in school is that when we want to share information or learn about something, we should strive to answer the questions Who, What, When, Where, Why, and How.  BARD is designed to help scientists discover the answer to these questions BioAssays, and to share the answers to these questions about their own work.


An assay definition describes the assay protocol as well as the biological system that the protocol seeks to investigate.  Describing the assay protocol consists of answering the questions of what is used in the protocol and how the protocol is conducted.  Specifying the biological system being studied answers the question of why the protocol is used.


Experiments describe the results of carrying out an assay protocol described by an assay definition.  As such, each experiment is associated with one - and only one - assay definition. Experiments indicate what compounds / samples where tested, what result types were measured and what were the values (numerical and otherwise) obtained, who ran the experiment, where and when it was run, and sometimes some further information about how it was carried out.


Taken together, an experiment and its assay definition answer the six major questions about BioAssays.  However, sometimes a series of experiments (and their corresponding assay definitions) are run and analyzed collectively to achieve a larger goal.  In BARD, a project is used to describe this situation.  The project diagram indicates what experiments were part of the project, and the order in which experiments were run (when).  Annotations on the project indicate who was responsible for it, and the goal of the project including biological system and/or disease being investigated (why), and what was the result of the project.


By using a combination of the assay definition, experiment, and project, a scientist who wishes to share information can answer the six major questions about their work.  Similarly, a scientist who wishes to search for answers to one or more of these questions can do so using a guided and faceted search.


To illustrate the above concepts, we can look at a specific assay definition:Luminescence Cell-Based Assay to Identify Compounds Cytotoxic to BJeLR RAS-Dependent Fibroblast” (ADID 3947).  The biology annotations indicate that this assay definition is run to investigate the process of cell death, specifically as it  relates to the protein GTPase HRas with a V12G substitution mutation (why).  It is a cell-based, cytotoxicity assay using ATP quantitation (how).   


An experiment associated with this assay definition is “Primary HTS CellTiter Glo viability assay in BJeLR cells, MLSMR library” (EID 3664).  During the course of this experiment, 303281 different compounds from the MLSMR compound  collection were tested (what).  The fundamental measurements made were percent activity and reproducibility; a compound has called a hit if it had percent activity greater than 40%.  Under this criteria, 516 of the tested compounds were active.  Joshua A. Bittker was the project lead for this experiment (who), and the experiment was carried at a single concentration but with two replicates (how).

Experiment 3664 was a primary screen and one of the first experiments (when) of the project Screen for RAS-Selective Lethal Compounds and VDAC Ligands” (PID 907).  The goal of the project was to investigate cancer, specifically through the GTPase HRas mechanism of positive regulation of cell death (why).  It was carried out at the Broad Institute (where) under grant number MH084117-01 (how); the assay provider was Brent Stockwel (who)l.  The project resulted in two probes:  ML162 and ML210 (what).

The above example is just a small part of the information contained in each assay definition, experiment and project, but it illustrates the basics of how BARD can help comprehensively answer questions about BioAssays.

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