Página 15 dos resultados de 6430 itens digitais encontrados em 0.035 segundos

‣ Computational discovery and analysis of metabolic pathways

Heath, Allison Park
Fonte: Universidade Rice Publicador: Universidade Rice
Português
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Finding novel or non-standard metabolic pathways, possibly spanning multiple species, has important applications in fields such as metabolic engineering, metabolic network analysis, and metabolic network reconstruction. Traditionally, this has been a manual process, but the large volume of metabolic data now available has created a need for computational tools to automatically identify biologically relevant pathways. This thesis presents new algorithms for automatically finding biologically meaningful linear and branched metabolic pathways in multi-genome scale metabolic networks. These algorithms utilize atom mapping data, which provides the correspondence between atoms in the substrates to atoms in the products of a chemical reaction, to find pathways which conserve a given number of atoms between desired start and target compounds. The first algorithm presented identifies atom conserving linear pathways by explicitly tracking atoms during an exploration of a graph structure constructed from the atom mapping data. The explicit tracking of atoms enables finding branched pathways because it provides automatic identification of the reactions and compounds through which atoms are lost or gained. The thesis then describes two algorithmic approaches for identifying branched metabolic pathways based upon atom conserving linear pathways. One approach takes one linear pathway at a time and attempts to add branches that connect loss and gain compounds. The other approach takes a group of linear pathways and attempts to merge pathways that move mutually exclusive sets of atoms from the start to the target compounds. Comparisons to known metabolic pathways demonstrate that atom tracking causes the algorithms to avoid many unrealistic connections...

‣ Towards Accurate Reconstruction of Phylogenetic Networks

Park, HyunJung
Fonte: Universidade Rice Publicador: Universidade Rice
Português
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Since Darwin proposed that all species on the earth have evolved from a common ancestor, evolution has played an important role in understanding biology. While the evolutionary relationships/histories of genes are represented using trees, the genomic evolutionary history may not be adequately captured by a tree, as some evolutionary events, such as horizontal gene transfer (HGT), do not fit within the branches of a tree. In this case, phylogenetic networks are more appropriate for modeling evolutionary histories. In this dissertation, we present computational algorithms to reconstruct phylogenetic networks from different types of data. Under the assumption that species have single copies of genes, and HGT and speciation are the only events through the course of evolution, gene sequences can be sampled one copy per species for HGT detection. Given the alignments of the sequences, we propose systematic methods that estimate the significance of detected HGT events under maximum parsimony (MP) and maximum likelihood (ML). The estimated significance aims at addressing the issue of overestimation of both optimization criteria in the search for phylogenetic networks and helps the search identify networks with the ``right" number of HGT edges. We study their performance on both synthetic and biological data sets. While the studies show very promising results in identifying HGT edges...

‣ Construção de filogenias baseadas em genomas completos; Phylogenies construction based on whole genomes

Karina Zupo de Oliveira
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 05/03/2010 Português
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Contexto: A classificação de espécies começou sendo determinada pelas características fenotípicas dos organismos. Logo que o DNA foi descoberto, o sistema de classificação passou também a utilizar-se das características genotípicas. Ao longo dos últimos anos, avanços científicos permitiram que fossem sequenciados genomas completos. A cada ano, o número de genomas completamente sequenciados aumenta, e, com isso, é cada vez maior o número de trabalhos que tentam utilizar-se do maior número possível de genes para comparar dois ou mais organismos com o objetivo de melhor entender o relacionamento entre as diversas espécies. Experimento: Este trabalho executa comparações de pares de cromossomos de um grupo de 10 genomas completos da família Vibrionaceae e um genoma completo da bactéria Escherichia coli como externo ao grupo. As homologias entre as proteínas são determinadas através da base de famílias Protein Clusters (NCBI). A seguir, arvores ultramétricas e a classificação COG das proteínas são utilizadas para resolver as paralogias correspondentes. Após isto, as proteínas únicas, que representam os eventos de perda e ganho de genes, são eliminadas, de forma a igualar o conteúdo dos cromossomos. Tipicamente...

‣ Why is Real-World Visual Object Recognition Hard?

DiCarlo, James J; Pinto, Nicolas; Cox, David Daniel
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Progress in understanding the brain mechanisms underlying vision requires the construction of computational models that not only emulate the brain's anatomy and physiology, but ultimately match its performance on visual tasks. In recent years, “natural” images have become popular in the study of vision and have been used to show apparently impressive progress in building such models. Here, we challenge the use of uncontrolled “natural” images in guiding that progress. In particular, we show that a simple V1-like model—a neuroscientist's “null” model, which should perform poorly at real-world visual object recognition tasks—outperforms state-of-the-art object recognition systems (biologically inspired and otherwise) on a standard, ostensibly natural image recognition test. As a counterpoint, we designed a “simpler” recognition test to better span the real-world variation in object pose, position, and scale, and we show that this test correctly exposes the inadequacy of the V1-like model. Taken together, these results demonstrate that tests based on uncontrolled natural images can be seriously misleading, potentially guiding progress in the wrong direction. Instead, we reexamine what it means for images to be natural and argue for a renewed focus on the core problem of object recognition—real-world image variation.; Molecular and Cellular Biology

‣ A Fast Algorithm for Computing Geodesic Distances in Tree Space

Owen, Megan; Provan, J. Scott
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Português
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Comparing and computing distances between phylogenetic trees are important biological problems, especially for models where edge lengths play an important role. The geodesic distance measure between two phylogenetic trees with edge lengths is the length of the shortest path between them in the continuous tree space introduced by Billera, Holmes, and Vogtmann. This tree space provides a powerful tool for studying and comparing phylogenetic trees, both in exhibiting a natural distance measure and in providing a Euclidean-like structure for solving optimization problems on trees. An important open problem is to find a polynomial time algorithm for finding geodesics in tree space. This paper gives such an algorithm, which starts with a simple initial path and moves through a series of successively shorter paths until the geodesic is attained.; Comment: 20 pages, 5 figures. Added new section on including common edges and leaf edge-lengths in the algorithm, clarified starting point for algorithm, added references, other minor improvements. To appear in IEEE/ACM Transactions on Computational Biology and Bioinformatics

‣ Developing a computational model of blood platelets with fluid dynamics applications

Viswanathan, Vijay; Pothapragada, Seetha
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 03/06/2012 Português
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This paper worked towards modeling blood platelets. Blood platelets, also known as thrombocytes, play a key role in blood clotting which is a vital human function. Furthermore, the role of these entities in strokes, myocardial infarctions, and coronary artery disease add to the importance of blood platelets. Analytical expressions for the structure of blood platelets in both their inactivated and activated states were developed, beginning with randomized two-dimensional models in polar coordinates. Weak frameworks in spherical and cylindrical systems were then created. Next, using rotational matrices to change the position and direction of a simple projection, useful, explicit, parametric system of equations were attained in three-dimensional Cartesian space which roughly approximate the structure of a blood platelet. Finally, a methodology to return the drag coefficient ($c_d$) for any inputted set of blood platelet images was designed. This method was incorporated into a C++ program returning the functional representation and drag coefficient of any given platelet. This work has primary applications in computational biophysics and fluid dynamics. Additionally, if the parameters of the model are extended, there could be ramifications in other areas of scientific modelling by connecting analytical expressions with instrinsic characteristics.; Comment: The author gratefully acknowledges the help of Seetha Pothapragada in aiding the production of this paper. This paper was submitted initially for the Siemens Competition for Math...

‣ The Complexity of Finding Multiple Solutions to Betweenness and Quartet Compatibility

Bonet, Maria Luisa; Linz, Simone; John, Katherine St.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Português
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We show that two important problems that have applications in computational biology are ASP-complete, which implies that, given a solution to a problem, it is NP-complete to decide if another solution exists. We show first that a variation of Betweenness, which is the underlying problem of questions related to radiation hybrid mapping, is ASP-complete. Subsequently, we use that result to show that Quartet Compatibility, a fundamental problem in phylogenetics that asks whether a set of quartets can be represented by a parent tree, is also ASP-complete. The latter result shows that Steel's \sc Quartet Challenge, which asks whether a solution to Quartet Compatibility is unique, is coNP-complete.; Comment: 25 pages, 7 figures

‣ An approach to describing and analysing bulk biological annotation quality: a case study using UniProtKB

Bell, Michael J.; Gillespie, Colin S.; Swan, Daniel; Lord, Phillip
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 10/08/2012 Português
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Motivation: Annotations are a key feature of many biological databases, used to convey our knowledge of a sequence to the reader. Ideally, annotations are curated manually, however manual curation is costly, time consuming and requires expert knowledge and training. Given these issues and the exponential increase of data, many databases implement automated annotation pipelines in an attempt to avoid un-annotated entries. Both manual and automated annotations vary in quality between databases and annotators, making assessment of annotation reliability problematic for users. The community lacks a generic measure for determining annotation quality and correctness, which we look at addressing within this article. Specifically we investigate word reuse within bulk textual annotations and relate this to Zipf's Principle of Least Effort. We use UniProt Knowledge Base (UniProtKB) as a case study to demonstrate this approach since it allows us to compare annotation change, both over time and between automated and manually curated annotations. Results: By applying power-law distributions to word reuse in annotation, we show clear trends in UniProtKB over time, which are consistent with existing studies of quality on free text English. Further...

‣ A Measure of Control for Secondary Cytokine-Induced Injury of Articular Cartilage: A Computational Study

Graham, Jason M
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 24/07/2013 Português
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In previous works, the author and collaborators establish a mathematical model for injury response in articular cartilage. In this paper we use mathematical software and computational techniques, applied to an existing model to explore in more detail how the behavior of cartilage cells is influenced by several of, what are believed to be, the most significant mechanisms underlying cartilage injury response at the cellular level. We introduce a control parameter, the radius of attenuation, and present some new simulations that shed light on how inflammation associated with cartilage injuries impacts the metabolic activity of cartilage cells. The details presented in the work can help to elucidate targets for more effective therapies in the preventative treatment of post-traumatic osteoarthritis.

‣ Computational paradigm for dynamic logic-gates in neuronal activity

Goldental, Amir; Guberman, Shoshana; Vardi, Roni; Kanter, Ido
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 15/04/2014 Português
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In 1943 McCulloch and Pitts suggested that the brain is composed of reliable logic-gates similar to the logic at the core of today's computers. This framework had a limited impact on neuroscience, since neurons exhibit far richer dynamics. Here we propose a new experimentally corroborated paradigm in which the truth tables of the brain's logic-gates are time dependent, i.e. dynamic logicgates (DLGs). The truth tables of the DLGs depend on the history of their activity and the stimulation frequencies of their input neurons. Our experimental results are based on a procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in-vitro. We demonstrate that the underlying biological mechanism is the unavoidable increase of neuronal response latencies to ongoing stimulations, which imposes a nonuniform gradual stretching of network delays. The limited experimental results are confirmed and extended by simulations and theoretical arguments based on identical neurons with a fixed increase of the neuronal response latency per evoked spike. We anticipate our results to lead to better understanding of the suitability of this computational paradigm to account for the brain's functionalities and will require the development of new systematic mathematical methods beyond the methods developed for traditional Boolean algebra.; Comment: 32 pages...

‣ Improved Core Genes Prediction for Constructing well-supported Phylogenetic Trees in large sets of Plant Species

AlKindy, Bassam; Al-Nayyef, Huda; Guyeux, Christophe; Couchot, Jean-François; Salomon, Michel; Bahi, Jacques M.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 23/04/2015 Português
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The way to infer well-supported phylogenetic trees that precisely reflect the evolutionary process is a challenging task that completely depends on the way the related core genes have been found. In previous computational biology studies, many similarity based algorithms, mainly dependent on calculating sequence alignment matrices, have been proposed to find them. In these kinds of approaches, a significantly high similarity score between two coding sequences extracted from a given annotation tool means that one has the same genes. In a previous work article, we presented a quality test approach (QTA) that improves the core genes quality by combining two annotation tools (namely NCBI, a partially human-curated database, and DOGMA, an efficient annotation algorithm for chloroplasts). This method takes the advantages from both sequence similarity and gene features to guarantee that the core genome contains correct and well-clustered coding sequences (\emph{i.e.}, genes). We then show in this article how useful are such well-defined core genes for biomolecular phylogenetic reconstructions, by investigating various subsets of core genes at various family or genus levels, leading to subtrees with strong bootstraps that are finally merged in a well-supported supertree.; Comment: 12 pages...

‣ Understanding Transcriptional Regulation Using De-novo Sequence Motif Discovery, Network Inference and Interactome Data

Rao, Arvind; Hero, Alfred O.; States, David J.; Engel, James Douglas
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 09/10/2007 Português
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Gene regulation is a complex process involving the role of several genomic elements which work in concert to drive spatio-temporal expression. The experimental characterization of gene regulatory elements is a very complex and resource-intensive process. One of the major goals in computational biology is the \textit{in-silico} annotation of previously uncharacterized elements using results from the subset of known, previously annotated, regulatory elements. The recent results of the ENCODE project (\emph{http://encode.nih.gov}) presented in-depth analysis of such functional (regulatory) non-coding elements for 1% of the human genome. It is hoped that the results obtained on this subset can be scaled to the rest of the genome. This is an extremely important effort which will enable faster dissection of other functional elements in key biological processes such as disease progression and organ development (\cite{Kleinjan2005},\cite{Lieb2006}. The computational annotation of these hitherto uncharacterized regions would require an identification of features that have good predictive value. In this work, we study transcriptional regulation as a problem in heterogeneous data integration, across sequence, expression and interactome level attributes. Using the example of the \textit{Gata2} gene and its recently discovered urogenital enhancers \cite{Khandekar2004} as a case study...

‣ GREAT: GRaphlet Edge-based network AlignmenT

Crawford, Joseph; Milenković, Tijana
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 19/10/2014 Português
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Network alignment aims to find regions of topological or functional similarities between networks. In computational biology, it can be used to transfer biological knowledge from a well-studied species to a poorly-studied species between aligned network regions. Typically, existing network aligners first compute similarities between nodes in different networks (via a node cost function) and then aim to find a high-scoring alignment (node mapping between the networks) with respect to "node conservation", typically the total node cost function over all aligned nodes. Only after an alignment is constructed, the existing methods evaluate its quality with respect to an alternative measure, such as "edge conservation". Thus, we recently aimed to directly optimize edge conservation while constructing an alignment, which improved alignment quality. Here, we approach a novel idea of maximizing both node and edge conservation, and we also approach this idea from a novel perspective, by aligning optimally edges between networks first in order to improve node cost function needed to then align well nodes between the networks. In the process, unlike the existing measures of edge conservation that treat each conserved edge the same, we favor conserved edges that are topologically similar over conserved edges that are topologically dissimilar. We show that our novel method...

‣ Bits from Biology for Computational Intelligence

Wibral, Michael; Lizier, Joseph T.; Priesemann, Viola
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 30/11/2014 Português
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Computational intelligence is broadly defined as biologically-inspired computing. Usually, inspiration is drawn from neural systems. This article shows how to analyze neural systems using information theory to obtain constraints that help identify the algorithms run by such systems and the information they represent. Algorithms and representations identified information-theoretically may then guide the design of biologically inspired computing systems (BICS). The material covered includes the necessary introduction to information theory and the estimation of information theoretic quantities from neural data. We then show how to analyze the information encoded in a system about its environment, and also discuss recent methodological developments on the question of how much information each agent carries about the environment either uniquely, or redundantly or synergistically together with others. Last, we introduce the framework of local information dynamics, where information processing is decomposed into component processes of information storage, transfer, and modification -- locally in space and time. We close by discussing example applications of these measures to neural data and other complex systems.

‣ "Pull moves" for rectangular lattice polymer models are not fully reversible

Györffy, Dániel; Závodszky, Péter; Szilágyi, András
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 01/10/2012 Português
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"Pull moves" is a popular move set for lattice polymer model simulations. We show that the proof given for its reversibility earlier is flawed, and some moves are irreversible, which leads to biases in the parameters estimated from the simulations. We show how to make the move set fully reversible.; Comment: 4 pages, 2 figures. To be published in IEEE/ACM Transactions on Computational Biology and Bioinformatics

‣ Unique Perfect Phylogeny Characterizations via Uniquely Representable Chordal Graphs

Gysel, Rob
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Português
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The perfect phylogeny problem is a classic problem in computational biology, where we seek an unrooted phylogeny that is compatible with a set of qualitative characters. Such a tree exists precisely when an intersection graph associated with the character set, called the partition intersection graph, can be triangulated using a restricted set of fill edges. Semple and Steel used the partition intersection graph to characterize when a character set has a unique perfect phylogeny. Bordewich, Huber, and Semple showed how to use the partition intersection graph to find a maximum compatible set of characters. In this paper, we build on these results, characterizing when a unique perfect phylogeny exists for a subset of partial characters. Our characterization is stated in terms of minimal triangulations of the partition intersection graph that are uniquely representable, also known as ur-chordal graphs. Our characterization is motivated by the structure of ur-chordal graphs, and the fact that the block structure of minimal triangulations is mirrored in the graph that has been triangulated.

‣ Complete RNA inverse folding: computational design of functional hammerhead ribozymes

Dotu, Ivan; Garcia-Martin, Juan Antonio; Slinger, Betty L.; Mechery, Vinodh; Meyer, Michelle M.; Clote, Peter
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 09/08/2014 Português
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Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields of research, poised to radically transform society in the 21st century. This paper concerns the synthetic design of ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using RNAiFold, we design ten cis-cleaving hammerhead ribozymes, all of which are shown to be functional by a cleavage assay. We additionally use RNAiFold to design a functional cis-cleaving hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computationally designed ribozymes may be correlated with positional entropy, ensemble defect, structural flexibility/rigidity and related measures. Artificial ribozymes have been designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential Enrichment); however, this appears to be the first purely computational design and experimental validation of novel functional ribozymes. RNAiFold is available at http://bioinformatics.bc.edu/clotelab/RNAiFold/.; Comment: 17 pages...

‣ Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect

Coquel, Anne-Sophie; Jacob, Jean-Pascal; Primet, Maël; Demarez, Alice; Dimiccoli, Mariella; Julou, Thomas; Moisan, Lionel; Lindner, Ariel B.; Berry, Hugues
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 08/03/2013 Português
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Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole...

‣ Statistical inference for template-based protein structure prediction

Peng, Jian
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 19/06/2013 Português
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Protein structure prediction is one of the most important problems in computational biology. The most successful computational approach, also called template-based modeling, identifies templates with solved crystal structures for the query proteins and constructs three dimensional models based on sequence/structure alignments. Although substantial effort has been made to improve protein sequence alignment, the accuracy of alignments between distantly related proteins is still unsatisfactory. In this thesis, I will introduce a number of statistical machine learning methods to build accurate alignments between a protein sequence and its template structures, especially for proteins having only distantly related templates. For a protein with only one good template, we develop a regression-tree based Conditional Random Fields (CRF) model for pairwise protein sequence/structure alignment. By learning a nonlinear threading scoring function, we are able to leverage the correlation among different sequence and structural features. We also introduce an information-theoretic measure to guide the learning algorithm to better exploit the structural features for low-homology proteins with little evolutionary information in their sequence profile. For a protein with multiple good templates...

‣ Transcriptional regulation: Effects of promoter proximal pausing on speed, synchrony and reliability

Boettiger, Alistair N.; Ralph, Peter L.; Evans, Steven N.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 11/03/2011 Português
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Recent whole genome polymerase binding assays have shown that a large proportion of unexpressed genes have pre-assembled RNA pol II transcription initiation complex stably bound to their promoters. Some such promoter proximally paused genes are regulated at transcription elongation rather than at initiation; it has been proposed that this difference allows these genes to both express faster and achieve more synchronous expression across populations of cells, thus overcoming molecular "noise" arising from low copy number factors. It has been established experimentally that genes which are regulated at elongation tend to express faster and more synchronously; however, it has not been shown directly whether or not it is the change in the regulated step {\em per se} that causes this increase in speed and synchrony. We investigate this question by proposing and analyzing a continuous-time Markov chain model of polymerase complex assembly regulated at one of two steps: initial polymerase association with DNA, or release from a paused, transcribing state. Our analysis demonstrates that, over a wide range of physical parameters, increased speed and synchrony are functional consequences of elongation control. Further, we make new predictions about the effect of elongation regulation on the consistent control of total transcript number between cells...