The code of codes or metacode is a microcosm where biological layers, as well as their codes, interact together allowing the continuity of information flow in organisms by increasing biological entities' complexity. Through this novel organic code, biological systems scale towards niches with higher informatic freedom building structures that increase the entropy in the universe. Code biology has developed a novel informational framework where biological entities strive themselves through the information flow carried out through organic codes consisting of two molecular or functional landscapes intertwined through arbitrary linkages via an adaptor whose nature is autonomous from molecular determinism. Here we will integrate genomic and epigenomic codes according to the evidence released in ENCODE (phase 3), psychENCODE and GTEx project, outlining the principles of the metacode, to address the continuous nature of biological systems and their inter-layered information flow. This novel complex metacode maps from very constrained sets of elements (i.e., regulation sites modulating gene expression) to new ones with greater freedom of decoding (i.e., a continuous cell phenotypic space). This leads to a new domain in code biology where biological systems are informatic attractors that navigate an energy metaspace through a complexity-noise balance, stalling in emergent niches where organic codes take meaning.
Keywords: Cell differentiation; Entropy; Information flow; Metacode.
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