, accepting internal error for random mutation producing homoplasy or loss of an actual synapomorphy.Aggregation modelingThere are a number of programs available for modeling -folding and aggregation of amyloidogenic peptides [61]. AmylPred is a consensus tool that predicts -folding and aggregation based on a set of five published methods and uses agreement of 2 or more methods for determining consensus [54]. PASTA predicts stabilizing sequences in -fibrillar structures using a calculation of the change of energy from pairing between amino acid sequences [53]. Regions that are known to form ordered -fibril structures have a PASTA energy less than 4. Using aligned amino acid sequences coded by Homo sapiens APP exons 16 and 17, we examined the corresponding A4 region across all taxa and used known secretase cleavage sites to determine the aligned sequences for submission to AmylPred and PASTA [62-64]. Where cleavage sites are not known from previous studies, boundaries were chosen based on similar species and sequences. In cases where there was no clear similarity, boundaries were extended to correspond with Homo sapiens A42. PASTA energies were collected until greater than 2 by sequential truncation of the C-terminus for each sequence.Tharp and Sarkar BMC Genomics 2013, 14:290 http://www.biomedcentral/1471-2164/14/Page 14 ofAdditional fileAdditional file 1: Figure S1. Phylogenetic Relationships among the Amyloid- Precursor Protein Gene Family from Baysian Inference. a, Phylogram showing the evolutionary relationships among the nucleotide sequences of the APP gene family. b, Phylogram for the corresponding protein sequences. Trees were generated by Bayesian inference methods and show posterior probability values are each node. Figure S2. Branch Supports for Phylogenetic Trees. Symmetric bootstrap re-sampling and Bremer supports, for nucleotide trees (a and b, respectively) and for amino acid trees (c and d, respectively).Dutasteride Table S1.Anti-Mouse CD3 Antibody Taxa Species Names and Sequence Accession Numbers.8. 9.10.11.Abbreviations A: Amyloid-; APP: APP, Amyloid- Precursor Protein; APPL-1: Amyloid- Precursor Protein-like 1 protein; APLP-1: Amyloid precursor like protein 1; APLP-2: Amyloid precursor like protein 2; APL-1: Amyloid precursor like 1 protein; BLS: Basolateral sorting signal; GFLD: Growth-factor-like domain; KPI: Kunitz-protease inhibitor; Mya: Million years ago.PMID:26780211 Competing interests INS and WGT do not have any conflicts of interest to disclose. Authors’ contributions INS and WGT conceived of and designed the study together. INS collected and aligned the sequences. WGT conducted the tree building and aggregation analyses. Both INS and WGT interpreted the results and drafted the manuscript together. Both authors read and approved the final manuscript. Acknowledgements This work was supported in part by a grant to I.N.S. from the National Library of Medicine (R01 LM009725). W.G.T. is supported by an individual fellowship award from the National Institute of Diabetes and Digestive and Kidney Diseases (F30 DK084605). Author details Center for Clinical and Translational Science, University of Vermont, Given Courtyard N309, 89 Beaumont Avenue, Burlington, VT 05405, USA. 2 Division of Endocrinology, Department of Medicine, University of Vermont, Given Courtyard N309, 89 Beaumont Avenue, Burlington, VT 05405, USA. 3 Department of Microbiology and Molecular Genetics, University of Vermont, Given Courtyard N309, 89 Beaumont Avenue, Burlington, VT 05405, USA. 4 Depa.