Thursday, December 11, 2014

Manuscript II - planning

I'm about to start writing my next manuscript. It's going to deal with patterns of gene expression in the placenta of F1 hybrids. I'm stalled a bit as I try to figure out exactly what questions I will be addressing and how I will go about discussing them in the manuscript. So, I'm hoping that writing this will help me flesh out my thoughts on what questions I'll be asking, why they are important, and how to address them.

First, all the questions I can think of that I can address with my data:

Is the histology of placentas abnormal in large or small hybrids? males or females?
Is gene expression disrupted in hybrid placentas?
How many genes show differential expression (DE)?
How many genes show DE between P. campbelli and P. sungorus (evolutionary changes)?
How many genes show DE between parents and hybrids (hybrid breakdown)?
How many genes show DE between cxs and SxC hybrids (could explain POE growth)?
How many genes are DE between males and females within each parent species?
How many genes are DE between males and females with the hybrids?
Are sex-specific effects prevalent in hamster hybrids?
For all these categories: what do those genes do? / Is there any functional enrichment for DE genes?
Do imprinted genes show DE?
Is imprinting disrupted (DI) in hybrids? Large, small, or both?
Does DI correlate with POE growth?
How often does disrupted imprinting correlate with differential expression?
Does the simple model of 'disrupted imprinting=2x increase in expression' hold?
Do paternally expressed genes show higher expression in large hybrids than small hybrids?
Do paternally expressed genes show higher expression in large hybrids than the parents?
Do maternally expressed genes show lower expression in large hybrids than small hybrids?
Do maternally expressed genes show lower expression in large hybrids than the parents?
What is happening on the X chromosome in hybrids?
Is X-linked expression disrupted?
Is X-linked expression correlated with abnormal growth?
Is there imprinted X inactivation (XCI) in hybrid placentas?
Is XCI disrupted?
Do any/many genes escape XCI? Which?
Does escape of XCI seem to have anything to do with POE growth?


Ok, that was more than I expected so that's good.
Now some organization.

My first thoughts are that the main question is what are patterns of expression in hybrid placentas and do they reflect a possible basis for parent-of-origin growth? This has three main sub-questions which are (1) what are the patterns of differential expression in hybrid placenta? (2) what is the pattern of imprinting in hybrid placenta? and (3) what is the overlap between DE and DI in hybrids?

So far, this sounds really descriptive and one of the strengths of my project is that I have a couple really strong a priori predictions about disrupted expression and imprinting and the size of the hybrids. Therefore, I think I should be able to motivate this in a more hypothesis-driven manner, rather than just as a simple description of expression patterns.

To do that, I need to lay out the prediction of gene expression.

To be continued...