The “Missing” Proteome: Undetected Proteins, Not-Translated Transcripts, and Untranscribed Genes

The
Chromosome-centric Human Proteome Project aims at characterizing
the expression of proteins encoded in each chromosome at the tissue,
cell, and subcellular levels. The proteomic profiling of a particular
tissue or cell line commonly results in a substantial portion of proteins
that are not observed (the “missing” proteome). The
concurrent transcriptome profiling of the analyzed tissue/cells samples
may help define the set of untranscribed genes in a given type of
tissue or cell, thus narrowing the size of the “missing”
proteome and allowing us to focus on defining the reasons behind undetected
proteins, namely, whether they are technical (insufficient sensitivity
of protein detection) or biological (correspond to not-translated
transcripts). We believe that the quantitative polymerase chain reaction
(qPCR) can provide an efficient approach to studying low-abundant
transcripts related to undetected proteins due to its high sensitivity
and the possibility of ensuring the specificity of detection via the
simple Sanger sequencing of PCR products. Here we illustrated the
feasibility of such an approach on a set of low-abundant transcripts.
Although inapplicable to the analysis of whole transcriptome, qPCR
can successfully be utilized to profile a limited cohort of transcripts
encoded on a particular chromosome, as we previously demonstrated
for human chromosome 18.