In Part 3 of this gene expression module, we're focusing on the curated DataSets database
in GEO, the Gene Expression Omnibus.
We first need the data, and briefly, this is what GEO wants from a submitter. What we
might call metadata goes into a GEO series record. The numerical data for each sample
is supplied as a Sample record. In our example, Dr. Pitroda submits 4 sample records. And
a description of the array goes into a Platform record.
This information ends up in the GEO DataSets database. Dr. Pitroda can locate the data
using the series number that was assigned to his submission. And, of course, this database
can be searched with text terms just like other NCBI databases.
Using the GSE accession retrieved 6 records. One is the Series -- the description of the
study. One is the platform, in this case a commercial array from Affymetrix. And the
other 4 are sample records, only one is shown here.
It is the sample record that contain the data tables.
I'm going to take a slight detour to explain a situation you might run into.
This is a view of the filter section on the right side of our search results page. We
know that the data can be found in the DataSets database, yet there is no DataSet record.
This is because the study has not yet been curated.
Let's extend our detour to talk about the concept of curation in GEO.
You may know, for example, that redundant GenBank sequences are curated into RefSeqs,
or reference sequences. This does not happen in GEO, mostly because gene expression studies
are just too variable.
Instead, GEO curators take studies and group the Sample, Series and Platform records into
a DataSet. This allows easier comparison of gene expression profiles in the whole study.
Let's look at an example of a curated DataSet.
Here we have a web display of records from a curated study. Originally Dr. R submitted
eight records: six samples, one platform and one series; and this family of records was
curated into a dataset record, GDS1964.
A GDS entry is easy to recognize because only curated records have these heatmap images.
It looks a bit like an array, but it is not. If you count the columns, there are six here,
which equals the number of samples.
Let's look at a GDS record in more detail.
This page acts as a sort of dashboard, with functions that allow data analysis and download.
One function is the Expression profiles button. Clicking that takes you to the GEO profiles
database, where you can see individual gene profiles.
Here we are focused in on Mef2a gene expression, where the profile shows relative expression
levels for the six samples, two controls marked by light green and the experimental samples
in darker green.
Remember that only curated DataSets benefit from these visualizations of the data. Given
the immense amount of data submitted to GEO, it is not possible to immediately curate all
studies, so the GEO group developed a tool called GEO2R that allows you to perform sample
comparison on your own for non-curated sets. I should point out that the statistics behind
GEO2R analysis are not identical to that in the curated records, but you can easily run
GEO2R on a curated study for comparison.
One more point about Geo profiles.
A big advantage in having curated records is the possibility to link to other resources.
For example, under Related information you can link to the Gene record or to Unigene.
Profile neighbors takes you to genes that have similar expression profiles, and Chromosome
neighbors identifies genes located near Mef2a.
You may also want to view the biological pathways for this gene product. The 'Find pathways'
button takes you to our Biosystems database...
Okay, let's return briefly to GEO curation to make one last point.
Currently, only microarray data are curated.
Of course, GEO accepts other types of data, such as that from epigenomics studies, but
this data ends up in the Epigenomics database.
This is one example of how DNA methylation data are presented in a curated epigenomics
record. We're looking at the region upstream of the Mef2a gene on chromosome 15, and this
track with the two blue blocks indicates the degree of methylation at those positions in
the genome.
Okay, that concludes this expression module. The next few slides summarize what we covered.
I'll scroll through those in blissful silence, but, first, don't hesitate to send questions
about any NCBI resources to this email address: info@ncbi.nlm.nih.gov