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- Creators: Biodesign Institute
- Member of: ASU Regents' Professors Open Access Works
Description
The Combined Activated Sludge-Anaerobic Digestion Model (CASADM) quantifies the effects of recycling anaerobic-digester (AD) sludge on the performance of a hybrid activated sludge (AS)-AD system. The model includes nitrification, denitrification, hydrolysis, fermentation, methanogenesis, and production/utilization of soluble microbial products and extracellular polymeric substances (EPS). A CASADM example shows that, while effluent COD and N are not changed much by hybrid operation, the hybrid system gives increased methane production in the AD and decreased sludge wasting, both caused mainly by a negative actual solids retention time in the hybrid AD. Increased retention of biomass and EPS allows for more hydrolysis and conversion to methane in the hybrid AD. However, fermenters and methanogens survive in the AS, allowing significant methane production in the settler and thickener of both systems, and AD sludge recycle makes methane formation greater in the hybrid system.
ContributorsYoung, Michelle (Author) / Marcus, Andrew (Author) / Rittmann, Bruce (Author) / Biodesign Institute (Contributor) / Swette Center for Environmental Biotechnology (Contributor)
Created2013-08-13
Description
Background
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
ContributorsZhang, Wenlu (Author) / Feng, Daming (Author) / Li, Rongjian (Author) / Chernikov, Andrey (Author) / Chrisochoides, Nikos (Author) / Osgood, Christopher (Author) / Konikoff, Charlotte (Author) / Newfeld, Stuart (Author) / Kumar, Sudhir (Author) / Ji, Shuiwang (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2013-12-28
Learning Sparse Representations for Fruit-Fly Gene Expression Pattern Image Annotation and Retrieval
Description
Background
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
Fruit fly embryogenesis is one of the best understood animal development systems, and the spatiotemporal gene expression dynamics in this process are captured by digital images. Analysis of these high-throughput images will provide novel insights into the functions, interactions, and networks of animal genes governing development. To facilitate comparative analysis, web-based interfaces have been developed to conduct image retrieval based on body part keywords and images. Currently, the keyword annotation of spatiotemporal gene expression patterns is conducted manually. However, this manual practice does not scale with the continuously expanding collection of images. In addition, existing image retrieval systems based on the expression patterns may be made more accurate using keywords.
Results
In this article, we adapt advanced data mining and computer vision techniques to address the key challenges in annotating and retrieving fruit fly gene expression pattern images. To boost the performance of image annotation and retrieval, we propose representations integrating spatial information and sparse features, overcoming the limitations of prior schemes.
Conclusions
We perform systematic experimental studies to evaluate the proposed schemes in comparison with current methods. Experimental results indicate that the integration of spatial information and sparse features lead to consistent performance improvement in image annotation, while for the task of retrieval, sparse features alone yields better results.
ContributorsYuan, Lei (Author) / Woodard, Alexander (Author) / Ji, Shuiwang (Author) / Jiang, Yuan (Author) / Zhou, Zhi-Hua (Author) / Kumar, Sudhir (Author) / Ye, Jieping (Author) / Biodesign Institute (Contributor) / Center for Evolution and Medicine (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor)
Created2012-05-23
Description
Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without the need for crystallization. In an effort to further develop the technique, we present a dataset of coherent soft X-ray diffraction images of Coliphage PR772 virus, collected at the Atomic Molecular Optics (AMO) beamline with pnCCD detectors in the LAMP instrument at the Linac Coherent Light Source. The diameter of PR772 ranges from 65–70 nm, which is considerably smaller than the previously reported ~600 nm diameter Mimivirus. This reflects continued progress in XFEL-based single-particle imaging towards the single molecular imaging regime. The data set contains significantly more single particle hits than collected in previous experiments, enabling the development of improved statistical analysis, reconstruction algorithms, and quantitative metrics to determine resolution and self-consistency.
ContributorsReddy, Hemanth K. N. (Author) / Yoon, Chun Hong (Author) / Aquila, Andrew (Author) / Awel, Salah (Author) / Ayyer, Kartik (Author) / Barty, Anton (Author) / Berntsen, Peter (Author) / Bielecki, Johan (Author) / Bobkov, Sergey (Author) / Bucher, Maximilian (Author) / Carini, Gabriella A. (Author) / Carron, Sebastian (Author) / Chapman, Henry (Author) / Daurer, Benedikt (Author) / DeMirci, Hasan (Author) / Ekeberg, Tomas (Author) / Fromme, Petra (Author) / Hajdu, Janos (Author) / Hanke, Max Felix (Author) / Hart, Philip (Author) / Hogue, Brenda (Author) / Hasseinizadeh, Ahmad (Author) / Kim, Yoonhee (Author) / Kirian, Richard (Author) / Kurta, Ruslan P. (Author) / Larsson, Daniel S. D. (Author) / Loh, N. Duane (Author) / Maia, Filipe R. N. C. (Author) / Mancuso, Adrian P. (Author) / Muhlig, Kerstin (Author) / Munke, Anna (Author) / Nam, Daewoong (Author) / Nettelblad, Carl (Author) / Ourmazd, Abbas (Author) / Rose, Max (Author) / Schwander, Peter (Author) / Seibert, Marvin (Author) / Sellberg, Jonas A. (Author) / Song, Changyong (Author) / Spence, John (Author) / Svenda, Martin (Author) / van der Schot, Gijs (Author) / Vartanyants, Ivan A. (Author) / Williams, Garth J. (Author) / Xavier, P. Lourdu (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Department of Physics (Contributor)
Created2017-06-27
Description
Anaerobic oxidation of methane (AOM) is an important process for understanding the global flux of methane and its relation to the global carbon cycle. Although AOM is known to be coupled to reductions of sulfate, nitrite, and nitrate, evidence that AOM is coupled with extracellular electron transfer (EET) to conductive solids is relatively insufficient. Here, we demonstrate EET-dependent AOM in a biofilm anode dominated by Geobacter spp. and Methanobacterium spp. using carbon-fiber electrodes as the terminal electron sink. The steady-state current density was kept at 11.0 ± 1.3 mA/m[superscript 2] in a microbial electrochemical cell, and isotopic experiments supported AOM-EET to the anode. Fluorescence in situ hybridization images and metagenome results suggest that Methanobacterium spp. may work synergistically with Geobacter spp. to allow AOM, likely by employing intermediate (formate or H[subscript 2])-dependent inter-species electron transport. Since metal oxides are widely present in sedimentary and terrestrial environments, an AOM-EET niche would have implications for minimizing the net global emissions of methane.
ContributorsGao, Yaohuan (Author) / Lee, Jangho (Author) / Neufeld, Josh D. (Author) / Park, Joonhong (Author) / Rittmann, Bruce (Author) / Lee, Hyung-Sool (Author) / Biodesign Institute (Contributor) / Swette Center for Environmental Biotechnology (Contributor)
Created2017-07-11
Description
Crystal structure determination of biological macromolecules using the novel technique of serial femtosecond crystallography (SFX) is severely limited by the scarcity of X-ray free-electron laser (XFEL) sources. However, recent and future upgrades render microfocus beamlines at synchrotron-radiation sources suitable for room-temperature serial crystallography data collection also. Owing to the longer exposure times that are needed at synchrotrons, serial data collection is termed serial millisecond crystallography (SMX). As a result, the number of SMX experiments is growing rapidly, with a dozen experiments reported so far. Here, the first high-viscosity injector-based SMX experiments carried out at a US synchrotron source, the Advanced Photon Source (APS), are reported. Microcrystals (5–20 µm) of a wide variety of proteins, including lysozyme, thaumatin, phycocyanin, the human A[subscript 2A] adenosine receptor (A[subscript 2A]AR), the soluble fragment of the membrane lipoprotein Flpp3 and proteinase K, were screened. Crystals suspended in lipidic cubic phase (LCP) or a high-molecular-weight poly(ethylene oxide) (PEO; molecular weight 8 000 000) were delivered to the beam using a high-viscosity injector. In-house data-reduction (hit-finding) software developed at APS as well as the SFX data-reduction and analysis software suites Cheetah and CrystFEL enabled efficient on-site SMX data monitoring, reduction and processing. Complete data sets were collected for A[subscript 2A]AR, phycocyanin, Flpp3, proteinase K and lysozyme, and the structures of A[subscript 2A]AR, phycocyanin, proteinase K and lysozyme were determined at 3.2, 3.1, 2.65 and 2.05 Å resolution, respectively. The data demonstrate the feasibility of serial millisecond crystallography from 5–20 µm crystals using a high-viscosity injector at APS. The resolution of the crystal structures obtained in this study was dictated by the current flux density and crystal size, but upcoming developments in beamline optics and the planned APS-U upgrade will increase the intensity by two orders of magnitude. These developments will enable structure determination from smaller and/or weakly diffracting microcrystals.
ContributorsMartin Garcia, Jose Manuel (Author) / Conrad, Chelsie (Author) / Nelson, Garrett (Author) / Stander, Natasha (Author) / Zatsepin, Nadia (Author) / Zook, James (Author) / Zhu, Lan (Author) / Geiger, James (Author) / Chun, Eugene (Author) / Kissick, David (Author) / Hilgart, Mark C. (Author) / Ogata, Craig (Author) / Ishchenko, Andrii (Author) / Nagaratnam, Nirupa (Author) / Roy Chowdhury, Shatabdi (Author) / Coe, Jesse (Author) / Subramanian, Ganesh (Author) / Schaffer, Alexander (Author) / James, Daniel (Author) / Ketwala, Gihan (Author) / Venugopalan, Nagarajan (Author) / Xu, Shenglan (Author) / Corcoran, Stephen (Author) / Ferguson, Dale (Author) / Weierstall, Uwe (Author) / Spence, John (Author) / Cherezov, Vadim (Author) / Fromme, Petra (Author) / Fischetti, Robert F. (Author) / Liu, Wei (Author) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / Department of Physics (Contributor)
Created2017-05-24
Description
A two-patch mathematical model of Dengue virus type 2 (DENV-2) that accounts for vectors’ vertical transmission and between patches human dispersal is introduced. Dispersal is modelled via a Lagrangian approach. A host-patch residence-times basic reproduction number is derived and conditions under which the disease dies out or persists are established. Analytical and numerical results highlight the role of hosts’ dispersal in mitigating or exacerbating disease dynamics. The framework is used to explore dengue dynamics using, as a starting point, the 2002 outbreak in the state of Colima, Mexico.
ContributorsBichara, Derdei (Author) / Holechek, Susan (Author) / Velazquez-Castro, Jorge (Author) / Murillo, Anarina (Author) / Castillo-Chavez, Carlos (Author) / Simon M. Levin Mathematical, Computational and Modeling Sciences Center (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Biodesign Institute (Contributor) / Infectious Diseases and Vaccinology (Contributor) / School of Life Sciences (Contributor)
Created2016-08-05
Description
CTB-MPR is a fusion protein between the B subunit of cholera toxin (CTB) and the membrane-proximal region of gp41 (MPR), the transmembrane envelope protein of Human immunodeficiency virus 1 (HIV-1), and has previously been shown to induce the production of anti-HIV-1 antibodies with antiviral functions. To further improve the design of this candidate vaccine, X-ray crystallography experiments were performed to obtain structural information about this fusion protein. Several variants of CTB-MPR were designed, constructed and recombinantly expressed in Escherichia coli. The first variant contained a flexible GPGP linker between CTB and MPR, and yielded crystals that diffracted to a resolution of 2.3 Å, but only the CTB region was detected in the electron-density map. A second variant, in which the CTB was directly attached to MPR, was shown to destabilize pentamer formation. A third construct containing a polyalanine linker between CTB and MPR proved to stabilize the pentameric form of the protein during purification. The purification procedure was shown to produce a homogeneously pure and monodisperse sample for crystallization. Initial crystallization experiments led to pseudo-crystals which were ordered in only two dimensions and were disordered in the third dimension. Nanocrystals obtained using the same precipitant showed promising X-ray diffraction to 5 Å resolution in femtosecond nanocrystallography experiments at the Linac Coherent Light Source at the SLAC National Accelerator Laboratory. The results demonstrate the utility of femtosecond X-ray crystallography to enable structural analysis based on nano/microcrystals of a protein for which no macroscopic crystals ordered in three dimensions have been observed before.
ContributorsLee, Ho-Hsien (Author) / Cherni, Irene (Author) / Yu, HongQi (Author) / Fromme, Raimund (Author) / Doran, Jeffrey (Author) / Grotjohann, Ingo (Author) / Mittman, Michele (Author) / Basu, Shibom (Author) / Deb, Arpan (Author) / Dorner, Katerina (Author) / Aquila, Andrew (Author) / Barty, Anton (Author) / Boutet, Sebastien (Author) / Chapman, Henry N. (Author) / Doak, R. Bruce (Author) / Hunter, Mark (Author) / James, Daniel (Author) / Kirian, Richard (Author) / Kupitz, Christopher (Author) / Lawrence, Robert (Author) / Liu, Haiguang (Author) / Nass, Karol (Author) / Schlichting, Ilme (Author) / Schmidt, Kevin (Author) / Seibert, M. Marvin (Author) / Shoeman, Robert L. (Author) / Spence, John (Author) / Stellato, Francesco (Author) / Weierstall, Uwe (Author) / Williams, Garth J. (Author) / Yoon, Chun Hong (Author) / Wang, Dingjie (Author) / Zatsepin, Nadia (Author) / Hogue, Brenda (Author) / Matoba, Nobuyuki (Author) / Fromme, Petra (Author) / Mor, Tsafrir (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Department of Chemistry and Biochemistry (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Biodesign Institute (Contributor) / Infectious Diseases and Vaccinology (Contributor) / Department of Physics (Contributor)
Created2014-08-20
Description
Carbohydrates are one of the four main building blocks of life, and are categorized as monosaccharides (sugars), oligosaccharides and polysaccharides. Each sugar can exist in two alternative anomers (in which a hydroxy group at C-1 takes different orientations) and each pair of sugars can form different epimers (isomers around the stereocentres connecting the sugars). This leads to a vast combinatorial complexity, intractable to mass spectrometry and requiring large amounts of sample for NMR characterization. Combining measurements of collision cross section with mass spectrometry (IM–MS) helps, but many isomers are still difficult to separate. Here, we show that recognition tunnelling (RT) can classify many anomers and epimers via the current fluctuations they produce when captured in a tunnel junction functionalized with recognition molecules. Most importantly, RT is a nanoscale technique utilizing sub-picomole quantities of analyte. If integrated into a nanopore, RT would provide a unique approach to sequencing linear polysaccharides.
ContributorsIm, Jong One (Author) / Biswas, Sovan (Author) / Liu, Hao (Author) / Zhao, Yanan (Author) / Sen, Suman (Author) / Biswas, Sudipta (Author) / Ashcroft, Brian (Author) / Borges, Chad (Author) / Wang, Xu (Author) / Lindsay, Stuart (Author) / Zhang, Peiming (Author) / Biodesign Institute (Contributor) / Single Molecule Biophysics (Contributor) / College of Liberal Arts and Sciences (Contributor) / Department of Physics (Contributor) / School of Molecular Sciences (Contributor)
Created2016-12-21
Description
pH and fermentable substrates impose selective pressures on gut microbial communities and their metabolisms. We evaluated the relative contributions of pH, alkalinity, and substrate on microbial community structure, metabolism, and functional interactions using triplicate batch cultures started from fecal slurry and incubated with an initial pH of 6.0, 6.5, or 6.9 and 10 mM glucose, fructose, or cellobiose as the carbon substrate. We analyzed 16S rRNA gene sequences and fermentation products. Microbial diversity was driven by both pH and substrate type. Due to insufficient alkalinity, a drop in pH from 6.0 to ~4.5 clustered pH 6.0 cultures together and distant from pH 6.5 and 6.9 cultures, which experienced only small pH drops. Cellobiose yielded more acidity than alkalinity due to the amount of fermentable carbon, which moved cellobiose pH 6.5 cultures away from other pH 6.5 cultures. The impact of pH on microbial community structure was reflected by fermentative metabolism. Lactate accumulation occurred in pH 6.0 cultures, whereas propionate and acetate accumulations were observed in pH 6.5 and 6.9 cultures and independently from the type of substrate provided. Finally, pH had an impact on the interactions between lactate-producing and -consuming communities. Lactate-producing Streptococcus dominated pH 6.0 cultures, and acetate- and propionate-producing Veillonella, Bacteroides, and Escherichia dominated the cultures started at pH 6.5 and 6.9. Acid inhibition on lactate-consuming species led to lactate accumulation. Our results provide insights into pH-derived changes in fermenting microbiota and metabolisms in the human gut.
ContributorsIlhan, Zehra (Author) / Marcus, Andrew (Author) / Kang, Dae-Wook (Author) / Rittmann, Bruce (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor) / Swette Center for Environmental Biotechnology (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Fundamental and Applied Microbiomics (Contributor) / Ira A. Fulton Schools of Engineering (Contributor) / School of Sustainable Engineering and the Built Environment (Contributor)
Created2017-05-03