当前位置： SCI文献检索 > BMC GENOMICS期刊下所有文献 > Identification of sequences common to more than one therapeutic target to treat complex diseases: simulating the high variance in sequence interactivity evolved to modulate robust phenotypes.

Identification of sequences common to more than one therapeutic target to treat complex diseases: simulating the high variance in sequence interactivity evolved to modulate robust phenotypes.

Abstract：

BACKGROUND:Genome-wide association studies show that most human traits and diseases are caused by a combination of environmental and genetic causes, with each one of these having a relatively small effect. In contrast, most therapies based on macromolecules like antibodies, antisense oligonucleotides or peptides focus on a single gene product. On the other hand, complex organisms seem to have a plethora of functional molecules able to bind specifically to multiple genes or genes products based on their sequences but the mechanisms that lead organisms to recruit these multispecific regulators remain unclear. RESULTS:The mutational biases inferred from the genomic sequences of six organisms show an increase in the variance of sequence interactivity in complex organisms. The high variance in the interactivity of sequences presents an ideal evolutionary substrate to recruit sequence-specific regulators able to target multiple gene products. For example, here it is shown how the 3'UTR can fluctuate between sequences likely to be complementary to other sites 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 key pathways in human disorders, such as cancer and immune diseases. This resource will be accessible to the community at www.wikisequences.org . CONCLUSIONS:This study describes and encourages the adoption of the same multitarget strategy (e.g., miRNAs, Hsp90) that has evolved in organisms to modify complex traits to treat diseases with robust 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 evolution of regulators able to interact to multiple gene products and modulate robust phenotypes. The identification of sequences common to more than one therapeutic target carried out in this study could facilitate the design of new multispecific methods able to modify simultaneously key pathways to treat complex diseases.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Varela MA

doi

10.1186/s12864-015-1727-6

subject

Has Abstract

pub_date

2015-07-18 00:00:00

pages

530

issn

1471-2164

pii

10.1186/s12864-015-1727-6

journal_volume

pub_type

杂志文章

在线工具

Identification of sequences common to more than one therapeutic target to treat complex diseases: simulating the high variance in sequence interactivity evolved to modulate robust phenotypes.