Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016) [1].

determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer's disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over-and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article "Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry" (Minjarez et al., 2016) [1].
& Data provide information of over-and sub-expressed polypeptides found in common in all Alzheimer's disease brains in relation to diseases and biofunctions in which they might be involved according to IPA database.
Data can be used in further studies to gain insight into the different affected pathways or networks, or into the role of each identified protein using cellular or whole organism models of Alzheimer's disease.
Data provide insight of putative biomarkers found in Alzheimer's disease brains and open the possibility to explore their expression level in a bigger number of brains with Alzheimer's disease in comparison to normal brains to validate them as possible biomarkers, as well as in serum of CSF samples.

Data
The data provides a list of identified 721 iTRAQ-labeled proteins with at least one peptide with Z95% in confidence ( Table 1). Polypeptides that changed in their expression levels were classified according to diseases and biofunctions with the IPA software ( Table 2) and analyzed with IPA Core I into different functional networks (Figs. 1-3). We included the mapping of proteins with differential expression into metabolic (Fig. 4) and oxidative phosphorylation (Fig. 5) processes, and determined different interaction networks using IntAct (Figs. 6 and 9) and BioGRID (Figs. 7, 8 and 10-13) databases. Fig. 1. IPA functional network of differentially expressed proteins found in all brains with Alzheimer's disease through IPA Core I analyses related with (i) Free Radical Scavenging, (ii) Neurological Disease, (iii) Cancer, and (iv) Cell Death and Survival. Different shapes, indicating the functional class to which they belong, represent proteins. Molecules in red are overexpressed polypeptides, whilst those green molecules correspond to subexpressed proteins. IPA incorporated molecules in grey, which are not specified, into the networks through relationships with other molecules. Molecular relationships between polypeptides are indicated with lines. A continuous line illustrates a direct interaction and a dotted line is used for indirect interactions. Proteins, whose expression is age-dependent, are labeled with a star (red and blue for over-and sub-expressed, respectively).

Experimental design, materials and methods
The analyses performed in this data article were focused on the over-or sub-expressed proteins that changed in their expression level in Z15% or r15%, respectively.

IPA Core Analysis of proteins that changed in their expression level in all Alzheimer's disease brains
For the classification of identified overexpressed and subexpressed proteins in all Alzheimer's disease brains [1] in diseases and biological functions, canonical pathways, molecular networks and the selection of putative candidates for biomarkers, we used the module Core Analysis and Biomarkers filter of the full version of the Ingenuity Pathway Analysis software (IPA, QIAGEN's Redwood City, www.qiagen.com/ingenuity). We performed one analysis named Core I. In this analysis we used tissues and primary cells, including nervous system, organ systems, and other tissues and primary cells. The filter also included cell lines of Central Nervous System (CNS), neuroblastoma, leukemia, osteosarcoma, melanoma, lymphoma, immune system, macrophage, lung, breast, hepatoma, pancreatic, kidney, myeloma, ovarian, cervical, prostate, teratocarcinoma and colon cancer, and other cell Activation Inhibition   4. Global view of the metabolic pathways of the KEGG database that were affected in brains with Alzheimer's disease. The overexpressed proteins are represented in red color and the subexpressed polypeptides in green. Those proteins whose expression is age-dependent are in red (overexpressed) and blue (subexpressed) rectangles (see Table 1 5. Localization of subexpressed proteins in the oxidative phosphorylation process obtained from the KEGG database. The localization of the subexpressed polypeptides in each complex of the respiratory chain is indicated in brilliant green color. We also show in brilliant green the subunits of the V-ATPase that were found subexpressed. Proteins, whose expression is agedependent, are labeled with a black star (see Table 2 in [1]).  Table 1 in [1] for data). lines, using a stringent filter. The Fisher's Exact Test was employed for the determination of the pvalue. It was considered as significant with values lower than 0.05. Analysis included the following parameters: (1) Ingenuity Knowledge Base (genes only), considering direct and indirect relationships.

IPA biomarker analysis
In order to select some putative biomarkers, we filtered all selected proteins through IPA software using only the Biomarkers I analyses. The parameters of Biomarkers filter I included all tissues and primary cells, and all cell lines, all diseases and all biomarkers application, and biomarkers diseases. It also included the following parameters: (1) human species, (2) all molecules type, and (3) all biofluids.    Table 2 in [1] for data).

Bioinformatics analyses in KEGG, IntAct and BioGRID databases
The proteins that showed a change in their expression levels in the three AD brains were mapped in the biochemical pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG) (http://www. genome.jp/kegg/). For the determination of interactions maps, sets of overexpressed and subexpressed proteins were submitted for their analysis to the IntAct Molecular Interaction Database at the European Bioinformatics Institute (http://www.ebi.ac.uk/intact/) [2]. To identify interactors that have been experimentally identified for selected overexpressed and subexpressed proteins, their IDs were submitted to the BioGRID database (Biological General Repository for Interaction Datasets, http://thebiogrid.org/) [3], using the current index version 3.4.133.