Dirichlet Mixtures, the Dirichlet Process, and the Structure of Protein Space

Abstract

The Dirichlet process is used to model probability distributions that are mixtures of an unknown number of components. Amino acid frequencies at homologous positions within related proteins have been fruitfully modeled by Dirichlet mixtures, and we use the Dirichlet process to derive such mixtures with an unbounded number of components. This application of the method requires several technical innovations to sample an unbounded number of Dirichlet-mixture components. The resulting Dirichlet mixtures model multiple-alignment data substantially better than do previously derived ones. They consist of over 500 components, in contrast to fewer than 40 previously, and provide a novel perspective on the structure of proteins. Individual protein positions should be seen not as falling into one of several categories, but rather as arrayed near probability ridges winding through amino acid multinomial space.

Unbiased Mitoproteome Analyses Confirm Non-canonical RNA, Expanded Codon Translations

“…These were detected by blast using default megablast alignment search parameters for input sequences consisting of in silico swinger transformed mitogenome versions [30], [31], [32], [33]. The detected GenBank sequences aligning with high identity levels with in silico produced swinger mitogenome versions (> 90% identity) were sequenced by the classical Sanger technology.…”

“…This is because transformations frequently occur systematically on sequences longer than 100 nucleotides. They seem produced by the same RNA polymerase as regular RNA, presumably after the RNA polymerase stabilizes in a hypothetical mode similar to that causing punctual nucleotide misinsertions [32], [33], [34]. This is also indicated by contiguity between regular and swinger sequences in the few detected chimeric RNAs, DNAs and peptides that consist of regular and swinger sequences [35], [36].…”

“…A ↔ C; and fourteen asymmetric exchanges, type X → Y → Z → X, e.g. A → C → G → A, [30], [31], [32], [33]), producing swinger RNAs.…”

“…Several independent evidences show that swinger polymerizations occasionally occur. (a) Swinger DNA has been detected [39], [40], in addition to swinger RNA [30], [31], [32], [33]. (b) Peptides corresponding to detected swinger RNAs also occur [23].…”

“…In addition, mitochondrial swinger RNA has been detected within datasets produced by classical Sanger sequencing [30], [31], [32], [33], and by massive next generation Illumina sequencing [23]. Swinger RNA properties converge between RNAs sequenced by these different methods [23].…”