Principal Investigator/Program Director Williams,Robert W.
Novelty of the informatics component
The bioinformatic novelty of this project is three-fold.
project has an absolutely unique research setting in the context of the
quantitative genetic dissection of the mouse CNS. Our atlases and
segmented data sets exist in a very complex informatics environment that
requires integration with the MBL, the iScope project, and the
Neurogenetics Tool Box. This integration across levels of analysis and
even across major research divisions (neuroscience and genetics) requires
a new level of sophistication in database design.
Second, we intend to make our tools accessible and malleable using web-based interfaces. Our goal is to allow neurogeneticists to modify and add to our brain models. If the pattern of in situ hybridization of a particular cDNA or mRNA defines a novel CNS compartment, then we need to allow this compartment to be added to our 3D model. The same applies to antibodies that label specific compartments, such as the anti-ChAT and anti-parvalbumin that we will test as part of the MBL. One can imagine an almost infinite number of ways in which molecular tags (whether epitopes recognized by antibodies or mRNAs) might segment the brain. This level of plasticity in models is definitely not yet the norm, and devising ways to make our models plastic over the Internet will be a significant challenge.Third, this project is associated with a classic Phase II problem: how does one move effectively from small demonstration projects (Phase I) to the massive high-throughput production mode that should ideally characterize more mature Phase II and III technology? In this project we need to segment brains and produce numbers at a pace that can keep up with a phenomenally productive Neurohistology Core that even without major funding has processed and digitized more than 600 brains. Gearing up to this challenge may seem like just a quantitative difference, but at this level of throughput, quantitative differences mandate qualitative changes in procedures.
Figure 1 is
a timeline for all proposed tasks as well as the role of personnel. In
this plan we outline procedures associated with each task and describe our
accuracy objectives, with details on how these objectives will be
assessed. Finally, we describe alternative tactics we will use if initial
methods do not meet our criteria.