Biology Reference
In-Depth Information
percentile ranks. Although order is preserved, the magnitude of differ-
ences between genes is lost, entailing at least some, and possibly very
great, loss of information. Combining ranks has been used as a strategy
in meta-analysis of genetic linkage studies.
21
Ranking has also been used in the microarray context.
22
The under-
lying idea is that since microarray data are noisy, the ranks may be rel-
atively more reliable than the actual measured values. This view is
somewhat undermined by the fact that the stability of the ranking
depends on the rank, the differences between underlying values, and
the sample size. It also ignores that the measure ranked in the original
analysis will also affect the ordering, and that independent studies may
well have used different statistics. The method does, however, take care
of the problem of different measurement types and scales for different
platforms.
We show below that platform noncommensurability can be handled by
transforming to a relevant test statistic. Thus, methods combining ranks
would only seem desirable if the sole information available from each study
is a list of ranked genes without any numerical measurement.
5.7. Combining Decisions
At the crudest level, we can combine the results of statistical hypothesis
tests. That is, rather than combining the
p
-values for the tests, we can
combine the resulting decisions based on some threshold for significance.
This Venn diagram method looks for overlap between lists of significant
genes across studies. A combined list of genes can be ranked based on
vote counting or formed based on repeated significance across studies.
Tools to carry out this type of procedure have been created for microarray
studies.
23,24
This method was proposed over 50 years ago.
25
Requiring all tests
to individually satisfy a significance criterion was shown to be inadmissi-
ble for testing an exponential family parameter,
26
and in general does
not appear to have very good power properties.
27
Yet, despite rather
poor performance, this method is intuitive and seems to be widely used.
