Experimental Design

Question:

For Alzheimer's Disease (AD), is there any indication of protein mis-folding phenomena and are there any similarities and differences across different species' gene sequences?

Hypothesis:

There should exist protein mis-folding phenomena, as indicated by amino acid residual differences, and there should exist similarities and differences across different species' gene sequences for Alzheimer's Disease (AD), denoted by conceptual analyses of orthologs and phenologs, clustering analysis, and an interaction network.

Materials and Methods:

Clustering across Amino Acid Frequencies

Clustering is done via Morpheus a versatile matrix visualization and analysis software. The dataset can be viewed as a heat map and further interactive tools such as filtration and algorithms can be applied to analyze the data. Amino acid frequencies of Alzheimer's risk increasing proteins were analyzed.

Pairwise Sequence Alignment

Pairwise Sequence Alignment is performed using EMBL-EBI's EMBOSS Water, which utilizes the Smith-Waterman algorithm (modified for speed enhancements) in order to calculate the local alignment of two inputted sequences.

Interaction Network - BioGrid

An Interaction Network is created using BioGRID 3.4 and the Gene/Identifier Search across all organisms.

InParanoid Ortholog Groups with InParalogs Creator

Ortholog groups are constructed using the InParanoid program which consists of using pairwise similarity scores (calculated using NCBI-Blast) between two complete proteomes.

Phenologs

Phenologs are created by using the Entrez gene identifier for APOE; all identified model organism/mutational phenotypes that show any overlap with the input set of the genes, ranked according to their hypergeometric probability scores, are returned.

Databases

UniProt/SwissProt/NextProt

Provides the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information. Database was used to pull the DNA sequences of various Alzheimer's risk increasing proteins.

OMIM

An online catalog of human genes and genetic disorders. Database was used to pull information about APOE e4.

Links with access to databases/software are below: