Project task 1

As part of an on-going research project in to mouse craniofacial development a developmental biologist has come to you to help interpret their microarray results.

Using micro-dissection techniques they have separated out three prominence's (Maxillary, Mandibular and Frontonasal) implicated in facial development and have repeated this for a number of time points during development (E10.5, E11, E11.5, E12, E12.5), resulting in a very comprehensive microarray data set.

They have identified 45 genes (See HeatMap and gene list below) which as a group are up regulated in the Mandibule from days E11 – E12.5 (first column of heatmap), are also up regulated in the Maxillary prominence at day E12.5 (second column of heatmap), and have unchanged expression in the Frontonasal prominence (third column of heatmap).

Gene List (45 Genes):

Ablim3
Acta1
Acta2
Actc1
Actn2
Actn3
Agtr2
Apobec2
Casq2
Cav3
Cdh15
Chrnb1
Chrng
Csrp3
Des
E430002G05Rik
Fndc5
Hoxa2
Itgb1bp2
Meox1
Msc
Mybph
Myh7
Myl4
Mylpf
Myod1
Myog
Myot
Myoz2
Nrk
P2ry1
P2ry6
Pitx3
Rapsn
Rxrg
Ryr1
Thbs4
Tnnc1
Tnnc2
Tnnt1
Tnnt2
Tnnt3
Trim63
Ttn
Zim1

Your job is to generate a hypothesis (or more than one) that explans why these genes are grouped together, and why these particular expression changes occurred at these times in these tissues.

This is real data from a real experiment. We don't know what the right answer is, but we have some hypotheses of our own and know a lot about these genes and their interactions. The purpose of this exercise is to see how well you can exploit existing knowledge sources to generate good potential explanations of results of high throughput experiments, one of the key research agendas in computational biology.

This is a difficult and open-ended task, but like most real research tasks, you have a limited amount of time to complete it. You must plan carefully to make sure that you use the limited time available as efficiently as you can.

The first part of this assignment is to develop your research plan. Start by being as explicit as you can about your goal(s) for the work. It is sometimes helpful to think about what figures you would like to have in the paper you write at the end of the project: what results will you need to populate the figures you would like to produce? Then consider what information you will need (which biological databases might have relevant information?) and create goals for knowledge -- what will you look up, and where? Consider possible problems that might arise, and what alternative tactics you might use to address them. Once you have the data you desire, what tools will you use to analyze, process or visualize it? Again, consider possible problems and alternative tactics. Finally--and very important--how will you evaluate the results of your efforts? What evidence will you produce that your results are complete and correct? How can you tell?

As a reminder, here are the NIH criteria for judging a research plan:

Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

You should produce a short (about 2 pages or so) research plan to address this problem. Please submit your plans via email to Hannah by the start of class on Tuesday, September 25, and come to class prepared to present and discuss these plans.

Then, revise and adjust your plan based on the class discussion, and start work. An approximately 8 page paper reporting your results will be due Thursday, October 4.