Analysis of Protein Sequences Using Time Frequency and Kolmogorov-Smirnov Methods

The plethora of genomic data currently available has resulted in a search for new algorithms and analysis techniques to interpret genomic data. In this two-fold study we explore techniques for locating critical amino acid residues in protein sequences and for estimating the similarity between proteins. We demonstrate the use of the Short-Time Fourier Transform and the Continuous Wavelet Transform together with amino acid hydrophobicity in locating important amino acid domains in proteins and also show that the Kolmogorov-Smirnov statistic can be used as a metric of protein similarity

CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features

CTCF DNA binding sites are classified into distinct functional classes, with distinct biological properties, shedding light on the differing functional roles of CTCF binding

Conservation and divergence of known apicomplexan transcriptional regulons

<p>Abstract</p> <p>Background</p> <p>The apicomplexans are a diverse phylum of parasites causing an assortment of diseases including malaria in a wide variety of animals and lymphoproliferation in cattle. Little is known about how these varied parasites regulate their transcriptional regulons. Even less is known about how regulon systems, consisting of transcription factors and target genes together with their associated biological process, evolve in these diverse parasites.</p> <p>Results</p> <p>In order to obtain insights into the differences in transcriptional regulation between these parasites we compared the orthology profiles of putative malaria transcription factors across species and examined the enrichment patterns of four binding sites across eleven apicomplexans.</p> <p>About three-fifths of the factors are broadly conserved in several phylogenetic orders of sequenced apicomplexans. This observation suggests the existence of regulons whose regulation is conserved across this ancient phylum. Transcription factors not broadly conserved across the phylum are possibly involved in regulon systems that have diverged between species. Examining binding site enrichment patterns in light of transcription factor conservation patterns suggests a second mode via which regulon systems may diverge - rewiring of existing transcription factors and their associated binding sites in specific ways. Integrating binding sites with transcription factor conservation patterns also facilitated prediction of putative regulators for one of the binding sites.</p> <p>Conclusions</p> <p>Even though transcription factors are underrepresented in apicomplexans, the distribution of these factors and their associated regulons reflect common and family-specific transcriptional regulatory processes.</p

Computational Analysis of Constraints on Noncoding Regions, Coding Regions and Gene Expression in Relation to Plasmodium Phenotypic Diversity

Malaria-causing Plasmodium species exhibit marked differences including host choice and preference for invading particular cell types. The genetic bases of phenotypic differences between parasites can be understood, in part, by investigating constraints on gene expression and genic sequences, both coding and regulatory.We investigated the evolutionary constraints on sequence and expression of parasitic genes by applying comparative genomics approaches to 6 Plasmodium genomes and 2 genome-wide expression studies. We found that the coding regions of Plasmodium transcription factor and sexual development genes are relatively less constrained, as are those of genes encoding CCCH zinc fingers and invasion proteins, which all play important roles in these parasites. Transcription factors and genes with stage-restricted expression have conserved upstream regions and so do several gene classes critical to the parasite's lifestyle, namely, ion transport, invasion, chromatin assembly and CCCH zinc fingers. Additionally, a cross-species comparison of expression patterns revealed that Plasmodium-specific genes exhibit significant expression divergence.Overall, constraints on Plasmodium's protein coding regions confirm observations from other eukaryotes in that transcription factors are under relatively lower constraint. Proteins relevant to the parasite's unique lifestyle also have lower constraint on their coding regions. Greater conservation between Plasmodium species in terms of promoter motifs suggests tight regulatory control of lifestyle genes. However, an interspecies divergence in expression patterns of these genes suggests that either expression is controlled via genomic or epigenomic features not encoded in the proximal promoter sequence, or alternatively, the combinatorial interactions between motifs confer species-specific expression patterns

Computational approaches for studying transcriptional regulation in Plasmodium and other apicomplexan parasites

The apicomplexans are a phylum of protozoan parasites that contribute significantly to eukaryotic morbidity and mortality. As apicomplexans are phylogenetically set apart from other species, knowledge cannot be easily transferred to apicomplexans from classical model organisms. Knowledge of apicomplexan transcriptional regulation, in particular, remains elusive. In this thesis, comparative genomics approaches are utilized to identify and characterize transcriptional networks in Plasmodia and other apicomplexans. We implemented a conservation-based transcription factor binding site discovery approach to better understand transcriptional regulation in two newly sequenced Plasmodium genomes. Binding sites were found to be conserved in both core processes like catabolism and more parasite-specific ones like invasion. The conservation patterns of discovered binding sites suggest a link between sites and parasite phenotypic differences. The genetic bases of phenotypic differences can be understood, in part, by investigating constraints on three aspects of transcriptional networks—transcription factors, regulatory sequences and gene expression. To this end, we explored evolutionary constraints on Plasmodium sequence and expression via existing and novel approaches. We found that transcription factors have relatively less constrained coding regions than genes involved in processes like metabolism. This is consistent with the view that transcription factors and associated networks are diverging to support phenotypic differences. Transcription factors and genes important to the parasites lifestyle have conserved upstream regions suggestive of complex transcriptional control. Additionally, a cross-species expression comparison revealed that Plasmodium-specific genes, many of which are lifestyle genes, exhibit more expression divergence than less phyletically-restricted genes. This suggests that transcriptional networks involving these genes are modified to support disparate parasite lifestyles. To obtain a phylum-wide view of network divergence, we assessed conservation patterns of three experimentally verified Plasmodium transcription factor binding sites in eleven apicomplexans. None of the associated networks were conserved in ail species but two networks were conserved across disparate phylogenetic orders of apicomplexans. Combining the conservation analysis with discoveries from a study of transcription factor orthology patterns highlights two modes of network evolution in these parasites: (i) evolution of disparate transcription factors and (ii) rewiring of common binding sites and their factors to regulate disparate processes in different species

Computational approaches for studying transcriptional regulation in Plasmodium and other apicomplexan parasites

The apicomplexans are a phylum of protozoan parasites that contribute significantly to eukaryotic morbidity and mortality. As apicomplexans are phylogenetically set apart from other species, knowledge cannot be easily transferred to apicomplexans from classical model organisms. Knowledge of apicomplexan transcriptional regulation, in particular, remains elusive. In this thesis, comparative genomics approaches are utilized to identify and characterize transcriptional networks in Plasmodia and other apicomplexans. We implemented a conservation-based transcription factor binding site discovery approach to better understand transcriptional regulation in two newly sequenced Plasmodium genomes. Binding sites were found to be conserved in both core processes like catabolism and more parasite-specific ones like invasion. The conservation patterns of discovered binding sites suggest a link between sites and parasite phenotypic differences. The genetic bases of phenotypic differences can be understood, in part, by investigating constraints on three aspects of transcriptional networks—transcription factors, regulatory sequences and gene expression. To this end, we explored evolutionary constraints on Plasmodium sequence and expression via existing and novel approaches. We found that transcription factors have relatively less constrained coding regions than genes involved in processes like metabolism. This is consistent with the view that transcription factors and associated networks are diverging to support phenotypic differences. Transcription factors and genes important to the parasites lifestyle have conserved upstream regions suggestive of complex transcriptional control. Additionally, a cross-species expression comparison revealed that Plasmodium-specific genes, many of which are lifestyle genes, exhibit more expression divergence than less phyletically-restricted genes. This suggests that transcriptional networks involving these genes are modified to support disparate parasite lifestyles. To obtain a phylum-wide view of network divergence, we assessed conservation patterns of three experimentally verified Plasmodium transcription factor binding sites in eleven apicomplexans. None of the associated networks were conserved in ail species but two networks were conserved across disparate phylogenetic orders of apicomplexans. Combining the conservation analysis with discoveries from a study of transcription factor orthology patterns highlights two modes of network evolution in these parasites: (i) evolution of disparate transcription factors and (ii) rewiring of common binding sites and their factors to regulate disparate processes in different species

Analysis of a Campus-wide Wireless Network

Understanding usage patterns in wireless local-area networks (WLANs) is critical for those who develop, deploy, and manage WLAN technology, as well as those who develop systems and application software for wireless networks. This paper presents results from the largest and most comprehensive trace of network activity in a large, production wireless LAN. For eleven weeks we traced the activity of nearly two thousand users drawn from a general campus population, using a campus-wide network of 476 access points spread over 161 buildings. Our study expands on those done by Tang and Baker, with a significantly larger and broader population. We found that residential traffic..

Characterizing usage of a campus-wide wireless network

Wireless local-area networks (WLANs) are increasingly common, but little is known about how they are used. A clear understanding of usage patterns in real WLANs is critical information to those who develop, deploy, and manage WLAN technology, as well as those who develop systems and application software for wireless networks. This paper presents results from the largest and most comprehensive trace of network activity in a large, production wireless LAN. For eleven weeks we traced the activity of nearly two thousand users drawn from a general campus population, using a campus-wide network of 476 access points spread over 161 buildings. Our study expands on those done by Tang and Baker, with a significantly larger and broader population. We found that residential traffic dominated all other traffic, particularly in residences populated by newer students; students are increasingly choosing a wireless laptop as their primary computer. Although web protocols were the single largest component of traffic volume, network backup and file sharing contributed an unexpectedly large amount to the traffic. Although there was some roaming within a network session, we were surprised by the number of situations in which cards roamed excessively, unable to settle on one access point. Cross-subnet roams were an especial problem, because they broke IP connections, indicating the need for solutions that avoid or accommodate such roams.