Finally, special care has to be taken for the processing of large CCS which, due to their sheer size, usually are functionally heterogeneous.
Since interaction networks of septins are functionally crucial due to their signal-mediating role in cellular processes15, unraveling the septin 7 interactome in lymphocytes could contribute to a better understanding of septin 7 function.
Another example of SL is between BRCA1 and CCNE1, which although are not components of the same physical pathway, are functionally related due to their roles in the cell cycle and therefore broadly fit into our proposed model.
If we assume the 196uORF/1266 gene set are functionally important due to their conservation, cross-referencing with those previously annotated [ 27, 28] yields 365 genes – a significant proportion of the genome.
Cancer differentiation takes place because tumor-associated stromal cells are functionally defective due to their down-regulated expression of certain organ-restricted genes and genes in smooth muscle cell differentiation [ 7].
As a result, both fore- and hindlimbs can be described as three-segmented limbs arranged in a zig-zag-configuration with the most proximal elements (i.e., scapula, femur), the middle segments (i.e., brachium, crus) and the distal segments (antebrachium, pes) being functionally analogous due to their similar direction and amplitude of motion.
Due to their compact, structurally simple, and yet functionally complex genomes, ssDNA viruses such as MSV would be expected to have a low degree of mutation robustness [ 14, 68], such that the vast majority of arising mutations would be expected to be at least slightly deleterious.
We therefore used this rationale to test whether identifying coevolving pairs of sites could allow us to identify known functionally important domains due to their three-dimensional proximity.
As in other functionally relevant elements, and especially due to their crucial regulatory role based on base complementarity, few mutations are expected to occur in miRNAs.
This reduced ability to functionally classify singletons is likely due to their shorter length (mean 344 bp vs. 1,248 bp), which reduces the length and quality of sequence alignments that are possible, especially considering the stringent criterion employed.
