The more organized a system is, the more sophisticated are the mechanisms that bias the way in which tensions are released by mutations or the way in which these mutations are corrected or expressed to increase complexity

The more organized a system is, the more sophisticated are the mechanisms that bias the way in which tensions are released by mutations or the way in which these mutations are corrected or expressed to increase complexity. in the genome in the search for advantageous interactions. A library of nucleotide- and peptide-based tools was built using a script to search for candidates (e.g. peptides, antigens to raise antibodies or antisense oligonucleotides) to target sequences shared by important pathways in human disorders, such as cancer and immune diseases. This resource will be accessible to the community atwww.wikisequences.org. == Conclusions == This study describes and stimulates the adoption of the same multitarget strategy (e.g., miRNAs, Hsp90) that has developed in organisms to modify complex traits to treat diseases with strong pathological phenotypes. The increase in the variance of sequence interactivity detected in the human and mouse genomes when compared with less complex organisms could have expedited the development of regulators able to interact to multiple gene products and modulate strong phenotypes. The identification of sequences common to more than one therapeutic target carried out in this study could Loxapine Succinate facilitate the design of new multispecific methods able to change simultaneously important pathways to treat complex diseases. == Electronic supplementary material == The online version SKP2 of this article (doi:10.1186/s12864-015-1727-6) contains supplementary material, which is available to authorized users. Keywords:Antibody, Antisense oligonucleotide, Decoy, Interactivity, Multispecific == Background == Genome-wide association studies have established that most human traits and diseases are caused by a combination of environmental and genetic causes. The vast majority of these causes have relatively small effects on a particular trait. Such as, intelligence is highly heritable, but the variability of the trait corresponds to the additive nature of multiple genotypes and their interactions [1]. Potentially, very different allelic combinations could produce equally gifted individuals. Equally, many human diseases, Loxapine Succinate such as cancer, or immune disorders, should also fall into this polygenic category [2]. In contrast, many therapeutic methods focus on modulating the large quantity of a single gene product or Loxapine Succinate targeting a single receptor. Developing a single compound to target the gene that has the largest effect in most patients can be a good strategy in some cases. Nevertheless, even when the effect around the phenotype is sufficient, with time, the success of treatment can be hampered by the upregulation of pathways other than the one that is being targeted. Redundant pathways are very common in complex organisms, and some have been managed over millions of years [3]. During development, higher organisms have recruited multitarget regulatory elements that are capable of modifying these robust networks and reconcile maintaining functionality under mutational pressure with being able to rapidly adapt the phenotype to the environment. Of notice among these regulatory elements are microRNAs (miRNA) and warmth shock protein 90 (Hsp90). miRNAs are short RNA molecules (1924 nucleotides long)[4,5] that generally downregulate gene expression by guiding the RNA-induced silencing complex (RISC) to a number of complementary mRNAs. In fact, miRNAs have been shown to play a role in increasing the canalization and tunability of networks [68]. In contrast, Hsp90 stabilizes proteins after synthesis and exposure to warmth. Hsp90 has been described as an evolutionary capacitor that allows genomes to store genetic diversity in complex traits without exposing them to natural selection [9,10]. Recently, the development of therapies that modulate these multi-regulatory elements has been actively pursued, e.g., therapies modulating miRNA levels in malignancy [11,12] or in cardiovascular diseases [13,14]. Additionally, the inhibition of Hsp90 activity has also shown potential in multiple studies, mainly in malignancy research [1517]. The main caveat of modulating natural combinatory elements is that they can potentially target many mRNAs or proteins that are unrelated to the particular pathology of interest, causing off-target effects. Therefore, it would be ideal to design tailored multi-regulatory tools. The aim of this work was to study the strategy by which organisms change complex traits in order to inspire the design of new therapeutic tools that are able to alter strong disease phenotypes. First, we analyzed around the features of complex genomes Loxapine Succinate that maintain high variances in the interactivity of.