Tree reconciliation combined with subsampling improves large scale inference of orthologous group hierarchies

Background: An orthologous group (OG) comprises a set of orthologous and paralogous genes that share a last common ancestor (LCA). OGs are defined with respect to a chosen taxonomic level, which delimits the position of the LCA in time to a specified speciation event. A hierarchy of OGs expands on this notion, connecting more general OGs, distant in time, to more recent, fine-grained OGs, thereby spanning multiple levels of the tree of life. Large scale inference of OG hierarchies with independently computed taxonomic levels can suffer from inconsistencies between successive levels, such as the position in time of a duplication event. This can be due to confounding genetic signal or algorithmic limitations. Importantly, inconsistencies limit the potential use of OGs for functional annotation and third-party applications. Results: Here we present a new methodology to ensure hierarchical consistency of OGs across taxonomic levels. To resolve an inconsistency, we subsample the protein space of the OG members and perform gene tree-species tree reconciliation for each sampling. Differently from previous approaches, by subsampling the protein space, we avoid the notoriously difficult task of accurately building and reconciling very large phylogenies. We implement the method into a high-throughput pipeline and apply it to the eggNOG database. We use independent protein domain definitions to validate its performance. Conclusion: The presented consistency pipeline shows that, contrary to previous limitations, tree reconciliation can be a useful instrument for the construction of OG hierarchies. The key lies in the combination of sampling smaller trees and aggregating their reconciliations for robustness. Results show comparable or greater performance to previous pipelines. The code is available on Github at: https://github.com/meringlab/og_consistency_pipeline

생물정보학적 접근방법을 이용한 유전적 표지인자 탐색과 유전체데이터의 유용한 정보 발굴

학위논문 (석사)-- 서울대학교 대학원 : 협동과정 생물정보학전공, 2016. 2. 김희발.These studies are mainly focusing on the deciphering biologically meaningful information in genome sequences of living organisms using bioinformatics techniques. In chapter 2, I investigate the relationship between genomic composition and Berkshire pigs meat quality trait by scanning for signatures of positive selection in whole-genome sequencing data. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Results revealed several candidate genes involved in Berkshire meat qualitymost of these genes are involved in lipid metabolism and intramuscular fat deposition. In chapter 3, I construct the HGTree: database of horizontally transferred genes determined by tree reconciliation. In Bacteria and Archaea, Horizontal gene transfer (HGT) plays an important role in the acquisition of biological advantages such as virulence factor and antibiotic resistance and provides significant genetic diversity. It is important to have a well-defined database containing precise information about HGT events between Prokaryotes in order to understand prokaryotic evolution and discover genes which have led to adaptive genetic variation through HGT as opposed to processes such as mutation, natural selection, or genetic drift. The HGTree database provides putative genome-wide horizontal gene transfer information for 2,472 prokaryotic genomes by reconciling gene trees against species trees. The tree reconciliation method is considered to be a useful way to detect HGT events but has not been utilized extensively by existing databases because the method is computationally intensive and conceptually challenging. In this regard, HGTree represents a useful addition to the biological community, enabling quick and easy retrieval of information for HGT-acquired genes and better understanding of microbial taxonomy and evolution. The database is freely available and can be easily scaled and updated to keep pace with the rapid rise in genomic information.ABSTRACT 4 CONTENTS 7 LIST OF TABLES 9 LIST OF FIGURES 10 CHAPTER 1. LITERATURE REVIEW 12 1.1 Detecting positive selection 13 1.2 Detecting horizontal gene transfer 15 CHAPTER 2. EXPLORING EVIDENCE OF POSITIVE SELECTION REVEALS GENETIC BASIS OF MEAT QUALITY TRAITS IN BERKSHIRE PIGS THROUGH WHOLE GENOME SEQUENCING 19 2.1 Introduction 20 2.2 Material and methods 21 2.3 Results 27 CHAPTER 3. HGTREE: DATABASE OF HORIZONTALLY TRANSFERRED GENES DETERMINED BY TREE RECONCILIATION 54 3.1 Introduction 55 3.2 Material and Methods 56 3.3 Results 62 3.4 Discussion 67 REFERENCES 82 국문초록 97Maste

Horizontal Gene Transfer as an Indispensable Driver for Evolution of Neocallimastigomycota into a Distinct Gut-Dwelling Fungal Lineage

Survival and growth of the anaerobic gut fungi (AGF; Neocallimastigomycota) in the herbivorous gut necessitate the possession of multiple abilities absent in other fungal lineages. We hypothesized that horizontal gene transfer (HGT) was instrumental in forging the evolution of AGF into a phylogenetically distinct gut-dwelling fungal lineage. The patterns of HGT were evaluated in the transcriptomes of 27 AGF strains, 22 of which were isolated and sequenced in this study, and 4 AGF genomes broadly covering the breadth of AGF diversity. We identified 277 distinct incidents of HGT in AGF transcriptomes, with subsequent gene duplication resulting in an HGT frequency of 2 to 3.5% in AGF genomes. The majority of HGT events were AGF specific (91.7%) and wide (70.8%), indicating their occurrence at early stages of AGF evolution. The acquired genes allowed AGF to expand their substrate utilization range, provided new venues for electron disposal, augmented their biosynthetic capabilities, and facilitated their adaptation to anaerobiosis. The majority of donors were anaerobic fermentative bacteria prevalent in the herbivorous gut. This study strongly indicates that HGT indispensably forged the evolution of AGF as a distinct fungal phylum and provides a unique example of the role of HGT in shaping the evolution of a high-rank taxonomic eukaryotic lineage.IMPORTANCE The anaerobic gut fungi (AGF) represent a distinct basal phylum lineage (Neocallimastigomycota) commonly encountered in the rumen and alimentary tracts of herbivores. Survival and growth of anaerobic gut fungi in these anaerobic, eutrophic, and prokaryote-dominated habitats necessitates the acquisition of several traits absent in other fungal lineages. We assess here the role of horizontal gene transfer as a relatively fast mechanism for trait acquisition by the Neocallimastigomycota postsequestration in the herbivorous gut. Analysis of 27 transcriptomes that represent the broad diversity of Neocallimastigomycota identified 277 distinct HGT events, with subsequent gene duplication resulting in an HGT frequency of 2 to 3.5% in AGF genomes. These HGT events have allowed AGF to survive in the herbivorous gut by expanding their substrate utilization range, augmenting their biosynthetic pathway, providing new routes for electron disposal by expanding fermentative capacities, and facilitating their adaptation to anaerobiosis. HGT in the AGF is also shown to be mainly a cross-kingdom affair, with the majority of donors belonging to the bacteria. This study represents a unique example of the role of HGT in shaping the evolution of a high-rank taxonomic eukaryotic lineage

U.S. Marine Corps Equipment Readiness Information Tool: usage and decision-support for performance based logistics

MBA Professional ReportThe Marine Corps is transforming its automated logistics programs to meet the increasingly complex operational requirements of the 21st Century. One program that is part of this transformation is the Marine Corps Equipment Readiness Information Tool (MERIT). Our research analyzed: how can MERIT be used as a decision support tool for performance based logistics (PBL) and what areas of MERIT are recommended for improvement. Included in the analysis is a description of current readiness procedures used in the Marine Corps, providing a point of comparison for how well MERIT enables the logistics transformation. The basis of our analysis was user perceptions, assessed by a user survey and focus groups. The conclusions of our analysis determined: MERIT has not received official Marine Corps endorsement for its continued use; MERIT is a valuable material readiness information tool used by the Marine Corps; there is a general lack of understanding by users regarding MERIT's logical architecture and operation; and there is a lack of training on MERIT throughout the Marine Corps.http://archive.org/details/usmarinecorpsequ109459891Major, United States Marine CorpsCaptain, United States Marine CorpsApproved for public release; distribution is unlimited