Gustavo Souza

In this manuscript we describe Proteogenomics Viewer, a web‐based tool that collects MS peptide identification, indexes to genomic sequence and structure, assigns exon usage, reports the identified protein isoforms with genomic alignments and, most importantly, allows the inspection of MS2 information for proper peptide identification. It also provides all performed indexing to facilitate global analysis of the data. The relevance of such tool is that there has been an increase in the number of proteogenomic efforts to improve the annotation of both genomics and proteomics data, culminating with the release of the two human proteome drafts. It is now clear that mass spectrometry‐based peptide identification of uncharacterized sequences, such as those resulting from unpredicted exon joints or non‐coding regions, is still prone to a higher than expected false discovery rate. Therefore, proper visualization of the raw data and the corresponding genome alignments are fundamental for further data validation and interpretation.

The main question herein is about the extent that reductionist approach can reach higher-level explanation as well as predict behavior from lower level of systems organization when concerning stability. Starting from a theoretical discussion on the complex hierarchical organization of biological systems, we offer a variety of examples showing the interchanging between bottom-up and top-down events underlying the regulation of the system. Moreover, we discuss and illustrate with different examples, how system stability under externally changing conditions are reached from many strategies without a specific level of causation, highlighting the role of downward causation with upward causation. Finally, we would like to demonstrate that there should be no dogmas when it comes to causation in biological systems.