Download Sander van Riet 13 June Reviewer Gene co

Sander van Riet
13 June
Reviewer
Gene co-expression is widely used to find new associations between different genes. The paper of
IvIiev et al. uses this concept together with Protein Atlas project in order to identify new genes
associated with motile cilia. Data from 3 different regions known to harbour motile cilia obtained
from the GEO database were used. First they linked with already known motile cilia proteins
together with proteins form the database. Furthermore they looked at the consensus of the protein
expression and the differential co-expression in the different tissue. The proteins of interest were
then validated and characterized for novelty, up regulation, localization and functional annotation.
The main findings of the study comprise of numerous proteins which they have identified as
associated with motile cilia that were not known before. Furthermore they analysed the novel
proteins using data mining of MEDLINE using anni. This analyses shows cilium biogenesis,
intraflagellar transport and spermatogenesis to comprise of the top 71% of the hits. Even more
interesting are the findings concerning dyslexia, using this analyses method the DCDC2, DYX1C1 and
KIAA0319 proteins were found to be associated with cilia. These proteins were already known to be
associated with dyslexia however there function was not known. The findings of this paper
contribute to a better understanding of proteins involved in ciliopathies and the further mapping of
the human proteome also this paper shows the usefulness of gene association studies.
During the selection and enrichment of the proteins the program DAVID was used in order to
identify shared annotations whereas later in the project anni was used to identify linkage. If both
programs are going to be used isn’t it possible to do the analyses using both programs and
combining the data at each step as it is known that DAVID and anni can have different outputs.
Could it be possible to miss targets when first using DAVID and subsequently using anni.
Furthermore the localization scoring of the different proteins is done using protein atlas project.
However the paper is lacking an explanation whether this is done in an objective manner and
whether the antibodies are very specific. Regarding the same problem is table 4: the 23 negative hits
in cat. III are probably lower as there could be some false negatives, this suggests that the majority is
associated with motile cilia. Could it be possible that there are false positives and the actual number
of novel finds is lower? Could you use data which uses antibodies that have been validated?