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Brayton, K. A.

Publications and source records attributed to Brayton, K. A..

2 recordsLinked to original sources

Using an Optimal Set of Features with a Machine Learning-Based Approach to Predict Effector Proteins for Legionella pneumophila

Type IV secretion systems exist in a number of bacterial pathogens and are used to secrete effector proteins directly into host cells in order to change their environment making the environment hospitable for the bacteria. In recent years, several machine learning algorithms have been developed to predict effector proteins, potentially facilitating experimental verification. However, inconsistencies exist between their results. Previously we analysed the disparate sets of predictive features used in these algorithms to determine an optimal set of 370 features for effector prediction. This work focuses on the best way to use these optimal features by designing three machine learning classifiers, comparing our results with those of others, and obtaining de novo results. We chose the pathogen Legionella pneumophila strain Philadelphia-1, a cause of Legionnaires disease, because it has many validated effector proteins and others have developed machine learning prediction tools for it. While all of our models give good results indicating that our optimal features are quite robust, Model 1, which uses all 370 features with a support vector machine, has slightly better accuracy. Moreover, Model 1 predicted 760 effector proteins, more than any other study, 315 of which have been validated. Although the results of our three models agree well with those of other researchers, their models only predicted 126 and 311 candidate effectors.

bioinformatics

Whole Proteome Clustering of 2,307 Genomes Reveals Remarkable Conservation of Four Proteins Among Proteobacteria While Revealing Significant Annotation Issues

To explore the concept of a minimal gene set, we clustered 8.76 M protein sequences deduced from 2,307 completely sequenced Proteobacterial genomes. To our knowledge this is the first study of this scale. Clustering resulted in 707,311 clusters of which 224,442 ranged in size from 2 to 2,894 sequences. The resulting clusters allowed us to ask the question: Is a set of proteins conserved across all Proteobacteria? We chose four essential proteins, the chaperonin GroEL, DNA dependent RNA polymerase subunits beta and beta (RpoB/RpoB), and DNA polymerase I (PolA), representing fundamental cellular functions, and examined their distribution in the clusters. We found these proteins to be remarkably conserved. Although the groEL gene was universally conserved in all the organisms in the study, the protein was not represented in all the deduced proteomes. The genes for RpoB and RpoB were missing from two genomes and merged in 88 genomes, and the sequences were sufficiently divergent that they formed separate clusters for 18 RpoB proteins (seven clusters) and 14 RpoB proteins (three clusters). For PolA, 52 organisms lacked an identifiable sequence, and seven sequences were sufficiently divergent that they formed five separate clusters. Interestingly, organisms lacking an identifiable PolA and those with divergent RpoB/RpoB were almost all endosymbionts. Furthermore, we present a range of examples of annotation issues that caused the deduced proteins to be incorrectly represented in the proteome. These annotation issues represent a significant obstacle for high throughput analyses.

genomics