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1. Designing sensitive viral diagnostics with machine learning

Author

Metsky, Hayden C., Welch, Nicole L., Pillai, Priya P., Haradhvala, Nicholas J., Rumker, Laurie, Mantena, Sreekar, Zhang, Yibin B., Yang, David K., Ackerman, Cheri M., Weller, Juliane, Blainey, Paul C., Myhrvold, Cameron, Mitzenmacher, Michael, and Sabeti, Pardis C.

Published
2022
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2. Iron detection and remediation with a functionalized porous polymer applied to environmental water samples

Author

Lee, Sumin, Uliana, Adam, Taylor, Mercedes K, Chakarawet, Khetpakorn, Bandaru, Siva Rama Satyam, Gul, Sheraz, Xu, Jun, Ackerman, Cheri M, Chatterjee, Ruchira, Furukawa, Hiroyasu, Reimer, Jeffrey A, Yano, Junko, Gadgil, Ashok, Long, Gary J, Grandjean, Fernande, Long, Jeffrey R, and Chang, Christopher J

Subjects
Inorganic Chemistry, Chemical Sciences, Chemical sciences
Abstract

Iron is one of the most abundant elements in the environment and in the human body. As an essential nutrient, iron homeostasis is tightly regulated, and iron dysregulation is implicated in numerous pathologies, including neuro-degenerative diseases, atherosclerosis, and diabetes. Endogenous iron pool concentrations are directly linked to iron ion uptake from environmental sources such as drinking water, providing motivation for developing new technologies for assessing iron(ii) and iron(iii) levels in water. However, conventional methods for measuring aqueous iron pools remain laborious and costly and often require sophisticated equipment and/or additional processing steps to remove the iron ions from the original environmental source. We now report a simplified and accurate chemical platform for capturing and quantifying the iron present in aqueous samples through use of a post-synthetically modified porous aromatic framework (PAF). The ether/thioether-functionalized network polymer, PAF-1-ET, exhibits high selectivity for the uptake of iron(ii) and iron(iii) over other physiologically and environmentally relevant metal ions. Mössbauer spectroscopy, XANES, and EXAFS measurements provide evidence to support iron(iii) coordination to oxygen-based ligands within the material. The polymer is further successfully employed to adsorb and remove iron ions from groundwater, including field sources in West Bengal, India. Combined with an 8-hydroxyquinoline colorimetric indicator, PAF-1-ET enables the simple and direct determination of the iron(ii) and iron(iii) ion concentrations in these samples, providing a starting point for the design and use of molecularly-functionalized porous materials for potential dual detection and remediation applications.

Published
2019

3. Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., Zhu, Meilin, Hua, Catherine, Weller, Juliane, Mirhashemi, Marzieh Ezzaty, Nguyen, Tien G., Mantena, Sreekar, Bauer, Matthew R., Shaw, Bennett M., Ackerman, Cheri M., Thakku, Sri Gowtham, Tse, Megan W., Kehe, Jared, Uwera, Marie-Martine, Eversley, Jacqueline S., Bielwaski, Derek A., McGrath, Graham, Braidt, Joseph, Johnson, Jeremy, Cerrato, Felecia, Moreno, Gage K., Krasilnikova, Lydia A., Petros, Brittany A., Gionet, Gabrielle L., King, Ewa, Huard, Richard C., Jalbert, Samantha K., Cleary, Michael L., Fitzgerald, Nicholas A., Gabriel, Stacey B., Gallagher, Glen R., Smole, Sandra C., Madoff, Lawrence C., Brown, Catherine M., Keller, Matthew W., Wilson, Malania M., Kirby, Marie K., Barnes, John R., Park, Daniel J., Siddle, Katherine J., Happi, Christian T., Hung, Deborah T., Springer, Michael, MacInnis, Bronwyn L., Lemieux, Jacob E., Rosenberg, Eric, Branda, John A., Blainey, Paul C., Sabeti, Pardis C., and Myhrvold, Cameron

Published
2022
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4. Tuning the Color Palette of Fluorescent Copper Sensors through Systematic Heteroatom Substitution at Rhodol Cores

Author

Jia, Shang, Ramos-Torres, Karla M, Kolemen, Safacan, Ackerman, Cheri M, and Chang, Christopher J

Subjects
Prevention, Bioengineering, Generic health relevance, Animals, Color, Copper, Drug Design, Fluorescence, Fluorescent Dyes, HEK293 Cells, Heterocyclic Compounds, 3-Ring, Humans, Mice, Microscopy, Confocal, Microscopy, Fluorescence, Molecular Structure, Chemical Sciences, Biological Sciences, Organic Chemistry
Abstract

Copper is an essential nutrient for sustaining life, and emerging data have expanded the roles of this metal in biology from its canonical functions as a static enzyme cofactor to dynamic functions as a transition metal signal. At the same time, loosely bound, labile copper pools can trigger oxidative stress and damaging events that are detrimental if misregulated. The signal/stress dichotomy of copper motivates the development of new chemical tools to study its spatial and temporal distributions in native biological contexts such as living cells. Here, we report a family of fluorescent copper sensors built upon carbon-, silicon-, and phosphorus-substituted rhodol dyes that enable systematic tuning of excitation/emission colors from orange to near-infrared. These probes can detect changes in labile copper levels in living cells upon copper supplementation and/or depletion. We demonstrate the ability of the carbon-rhodol based congener, Copper Carbo Fluor 1 (CCF1), to identify elevations in labile copper pools in the Atp7a-/- fibroblast cell model of the genetic copper disorder Menkes disease. Moreover, we showcase the utility of the red-emitting phosphorus-rhodol based dye Copper Phosphorus Fluor 1 (CPF1) in dual-color, dual-analyte imaging experiments with the green-emitting calcium indicator Calcium Green-1 to enable simultaneous detection of fluctuations in copper and calcium pools in living cells. The results provide a starting point for advancing tools to study the contributions of copper to health and disease and for exploiting the rapidly growing palette of heteroatom-substituted xanthene dyes to rationally tune the optical properties of fluorescent indicators for other biologically important analytes.

Published
2018

5. Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system.

Author

Xiao, Tong, Ackerman, Cheri M, Carroll, Elizabeth C, Jia, Shang, Hoagland, Adam, Chan, Jefferson, Thai, Bao, Liu, Christine S, Isacoff, Ehud Y, and Chang, Christopher J

Subjects
Locus Coeruleus, Animals, Zebrafish, Copper, Norepinephrine, Biochemistry & Molecular Biology, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology
Abstract

The unusually high demand for metals in the brain, along with insufficient understanding of how their dysregulation contributes to neurological diseases, motivates the study of how inorganic chemistry influences neural circuitry. We now report that the transition metal copper is essential for regulating rest-activity cycles and arousal. Copper imaging and gene expression analysis in zebrafish identifies the locus coeruleus-norepinephrine (LC-NE) system, a vertebrate-specific neuromodulatory circuit critical for regulating sleep, arousal, attention, memory and emotion, as a copper-enriched unit with high levels of copper transporters CTR1 and ATP7A and the copper enzyme dopamine β-hydroxylase (DBH) that produces NE. Copper deficiency induced by genetic disruption of ATP7A, which loads copper into DBH, lowers NE levels and hinders LC function as manifested by disruption in rest-activity modulation. Moreover, LC dysfunction caused by copper deficiency from ATP7A disruption can be rescued by restoring synaptic levels of NE, establishing a molecular CTR1-ATP7A-DBH-NE axis for copper-dependent LC function.

Published
2018

6. Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease.

Author

Ackerman, Cheri M, Weber, Peter K, Xiao, Tong, Thai, Bao, Kuo, Tiffani J, Zhang, Emily, Pett-Ridge, Jennifer, and Chang, Christopher J

Subjects
Mitochondria, Animals, Zebrafish, Menkes Kinky Hair Syndrome, Disease Models, Animal, Copper, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Secondary Ion, Phenotype, Mutation, Nanotechnology, Laser Therapy, Photoreceptor Cells, Vertebrate, Multimodal Imaging, Copper-transporting ATPases, Copper-Transporting ATPases, Disease Models, Animal, Spectrometry, Mass, Electrospray Ionization, Secondary Ion, Photoreceptor Cells, Vertebrate, Analytical Chemistry, Chemical Sciences
Abstract

Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases. Here we combine metal imaging and optical imaging techniques at a variety of spatial resolutions to identify tissues and structures with altered copper levels in the Calamitygw71 zebrafish model of Menkes disease. Rapid profiling of tissue slices with LA-ICP-MS identified reduced copper levels in the brain, neuroretina, and liver of Menkes fish compared to control specimens. High resolution nanoSIMS imaging of the neuroretina, combined with electron and confocal microscopies, identified the megamitochondria of photoreceptors as loci of copper accumulation in wildtype fish, with lower levels of megamitochondrial copper observed in Calamitygw71 zebrafish. Interestingly, this localized copper decrease does not result in impaired photoreceptor development or altered megamitochondrial morphology, suggesting the prioritization of copper at sufficient levels for maintaining essential mitochondrial functions. Together, these data establish the Calamitygw71 zebrafish as an optically transparent in vivo model for the study of neural copper misregulation, illuminate a role for the ATP7A copper exporter in trafficking copper to the neuroretina, and highlight the utility of combining multiple imaging techniques for studying metals in whole organism settings with spatial resolution.

Published
2018

7. Copper signaling in the brain and beyond

Author

Ackerman, Cheri M and Chang, Christopher J

Subjects
Biochemistry and Cell Biology, Biological Sciences, Animals, Brain, Copper, Humans, Signal Transduction, cancer biology, copper signaling, copper transport, immunology, lipolysis, metal homeostasis, neurobiology, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition-metal signaling, where dynamic changes in transitional metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition-metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

Published
2018

10. In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

Author

Heffern, Marie C, Park, Hyo Min, Au-Yeung, Ho Yu, Van de Bittner, Genevieve C, Ackerman, Cheri M, Stahl, Andreas, and Chang, Christopher J

Subjects
Biochemistry and Cell Biology, Chemical Sciences, Biological Sciences, Nutrition, Chronic Liver Disease and Cirrhosis, Biomedical Imaging, Digestive Diseases, Liver Disease, Oral and gastrointestinal, Animals, Copper, Diet, High-Fat, Firefly Luciferin, Luminescent Agents, Luminescent Measurements, Male, Metallochaperones, Mice, Mice, Transgenic, Molecular Imaging, Non-alcoholic Fatty Liver Disease, metal homeostasis, molecular imaging, luciferin, metabolic liver disease, copper
Abstract

Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals. CCL-1 uses a selective copper(I)-dependent oxidative cleavage reaction to release d-luciferin for subsequent bioluminescent reaction with firefly luciferase. The probe can detect physiological changes in labile Cu+ levels in live cells and mice under situations of copper deficiency or overload. Application of CCL-1 to mice with liver-specific luciferase expression in a diet-induced model of nonalcoholic fatty liver disease reveals onset of hepatic copper deficiency and altered expression levels of central copper trafficking proteins that accompany symptoms of glucose intolerance and weight gain. The data connect copper dysregulation to metabolic liver disease and provide a starting point for expanding the toolbox of reactivity-based chemical reporters for cell- and tissue-specific in vivo imaging.

Published
2016

11. Copper regulates cyclic-AMP-dependent lipolysis

Author

Krishnamoorthy, Lakshmi, Cotruvo, Joseph A, Chan, Jefferson, Kaluarachchi, Harini, Muchenditsi, Abigael, Pendyala, Venkata S, Jia, Shang, Aron, Allegra T, Ackerman, Cheri M, Wal, Mark N Vander, Guan, Timothy, Smaga, Lukas P, Farhi, Samouil L, New, Elizabeth J, Lutsenko, Svetlana, and Chang, Christopher J

Subjects
Biochemistry and Cell Biology, Biological Sciences, 3T3-L1 Cells, Animals, Copper, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Type 3, Dose-Response Relationship, Drug, Lipolysis, Mice, Molecular Structure, Phosphodiesterase 3 Inhibitors, Structure-Activity Relationship, Medicinal and Biomolecular Chemistry, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores. Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue in a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype.

Published
2016

12. Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson’s Disease

Author

Lee, Sumin, Barin, Gokhan, Ackerman, Cheri M, Muchenditsi, Abigael, Xu, Jun, Reimer, Jeffrey A, Lutsenko, Svetlana, Long, Jeffrey R, and Chang, Christopher J

Subjects
Inorganic Chemistry, Chemical Sciences, Neurodegenerative, Neurosciences, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Animals, Copper, Disease Models, Animal, Hepatolenticular Degeneration, Mice, Molecular Structure, Polymers, Porosity, Sensitivity and Specificity, Sulfides, General Chemistry, Chemical sciences, Engineering
Abstract

Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson's and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson's disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications.

Published
2016

14. Massively multiplexed nucleic acid detection with Cas13

Author

Ackerman, Cheri M., Myhrvold, Cameron, Thakku, Sri Gowtham, Freije, Catherine A., Metsky, Hayden C., Yang, David K., and Ye, Simon H.

Subjects
Nucleic acids -- Physiological aspects -- Identification and classification, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples.sup.1-3 while simultaneously testing for many pathogens.sup.4-6. Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents.sup.7 self-organize in a microwell array.sup.8 to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health.sup.9-11. CRISPR-based nucleic acid detection is used in a platform that can simultaneously detect 169 human-associated viruses in multiple samples, providing scalable, multiplexed pathogen detection aimed at routine surveillance for public health., Author(s): Cheri M. Ackerman [sup.1] [sup.2] , Cameron Myhrvold [sup.1] [sup.3] , Sri Gowtham Thakku [sup.1] [sup.4] , Catherine A. Freije [sup.1] [sup.5] , Hayden C. Metsky [sup.1] [sup.6] , [...]

Published
2020
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15. Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., primary, Zhu, Meilin, additional, Hua, Catherine, additional, Weller, Juliane, additional, Mirhashemi, Marzieh Ezzaty, additional, Nguyen, Tien G., additional, Mantena, Sreekar, additional, Bauer, Matthew R., additional, Shaw, Bennett M., additional, Ackerman, Cheri M., additional, Thakku, Sri Gowtham, additional, Tse, Megan W., additional, Kehe, Jared, additional, Uwera, Marie-Martine, additional, Eversley, Jacqueline S., additional, Bielwaski, Derek A., additional, McGrath, Graham, additional, Braidt, Joseph, additional, Johnson, Jeremy, additional, Cerrato, Felecia, additional, Moreno, Gage K., additional, Krasilnikova, Lydia A., additional, Petros, Brittany A., additional, Gionet, Gabrielle L., additional, King, Ewa, additional, Huard, Richard C., additional, Jalbert, Samantha K., additional, Cleary, Michael L., additional, Fitzgerald, Nicholas A., additional, Gabriel, Stacey B., additional, Gallagher, Glen R., additional, Smole, Sandra C., additional, Madoff, Lawrence C., additional, Brown, Catherine M., additional, Keller, Matthew W., additional, Wilson, Malania M., additional, Kirby, Marie K., additional, Barnes, John R., additional, Park, Daniel J., additional, Siddle, Katherine J., additional, Happi, Christian T., additional, Hung, Deborah T., additional, Springer, Michael, additional, MacInnis, Bronwyn L., additional, Lemieux, Jacob E., additional, Rosenberg, Eric, additional, Branda, John A., additional, Blainey, Paul C., additional, Sabeti, Pardis C., additional, and Myhrvold, Cameron, additional

Published
2023
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16. Multiplexed detection of bacterial nucleic acids using Cas13 in droplet microarrays

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Thakku, Sri Gowtham, Ackerman, Cheri M, Myhrvold, Cameron, Bhattacharyya, Roby P, Livny, Jonathan, Ma, Peijun, Gomez, Giselle Isabella, Sabeti, Pardis C, Blainey, Paul C, Hung, Deborah T, Massachusetts Institute of Technology. Department of Biological Engineering, Thakku, Sri Gowtham, Ackerman, Cheri M, Myhrvold, Cameron, Bhattacharyya, Roby P, Livny, Jonathan, Ma, Peijun, Gomez, Giselle Isabella, Sabeti, Pardis C, Blainey, Paul C, and Hung, Deborah T

Abstract

Abstract Rapid and accurate diagnosis of infections is fundamental to individual patient care and public health management. Nucleic acid detection methods are critical to this effort, but are limited either in the breadth of pathogens targeted or by the expertise and infrastructure required. We present here a high-throughput system that enables rapid identification of bacterial pathogens, bCARMEN, which utilizes: (1) modular CRISPR-Cas13-based nucleic acid detection with enhanced sensitivity and specificity; and (2) a droplet microfluidic system that enables thousands of simultaneous, spatially multiplexed detection reactions at nanoliter volumes; and (3) a novel preamplification strategy that further enhances sensitivity and specificity. We demonstrate bCARMEN is capable of detecting and discriminating 52 clinically relevant bacterial species and several key antibiotic resistance genes. We further develop a simple proof of principle workflow using stabilized reagents and cell phone camera optical readout, opening up the possibility of a rapid point-of-care multiplexed bacterial pathogen identification and antibiotic susceptibility testing.

Published
2023

17. Designing sensitive viral diagnostics with machine learning

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Metsky, Hayden C, Welch, Nicole L, Pillai, Priya P, Haradhvala, Nicholas J, Rumker, Laurie, Mantena, Sreekar, Zhang, Yibin B, Yang, David K, Ackerman, Cheri M, Weller, Juliane, Blainey, Paul C, Myhrvold, Cameron, Mitzenmacher, Michael, Sabeti, Pardis C, Massachusetts Institute of Technology. Department of Biological Engineering, Metsky, Hayden C, Welch, Nicole L, Pillai, Priya P, Haradhvala, Nicholas J, Rumker, Laurie, Mantena, Sreekar, Zhang, Yibin B, Yang, David K, Ackerman, Cheri M, Weller, Juliane, Blainey, Paul C, Myhrvold, Cameron, Mitzenmacher, Michael, and Sabeti, Pardis C

Abstract

AbstractDesign of nucleic acid-based viral diagnostics typically follows heuristic rules and, to contend with viral variation, focuses on a genome’s conserved regions. A design process could, instead, directly optimize diagnostic effectiveness using a learned model of sensitivity for targets and their variants. Toward that goal, we screen 19,209 diagnostic–target pairs, concentrated on CRISPR-based diagnostics, and train a deep neural network to accurately predict diagnostic readout. We join this model with combinatorial optimization to maximize sensitivity over the full spectrum of a virus’s genomic variation. We introduce Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT), a system for automated design, and use it to design diagnostics for 1,933 vertebrate-infecting viral species within 2 hours for most species and within 24 hours for all but three. We experimentally show that ADAPT’s designs are sensitive and specific to the lineage level and permit lower limits of detection, across a virus’s variation, than the outputs of standard design techniques. Our strategy could facilitate a proactive resource of assays for detecting pathogens.

Published
2023

19. Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and SARS-CoV-2 variants

Author

Welch, Nicole L, primary, Zhu, Meilin, additional, Hau, Catherine, additional, Weller, Juliane, additional, Ezzaty Mirhashemi, Marzieh, additional, Mantena, Sreekar, additional, Nguyen, Tien G, additional, Shaw, Bennett, additional, Ackerman, Cheri M, additional, Thakku, Sri Gowtham, additional, Tse, Megan W, additional, Kehe, Jared, additional, Bauer, Matthew R, additional, Uwera, Maria-Martine, additional, Eversley, Jacqueline S, additional, Bielawski, Derek A, additional, McGrath, Graham, additional, Braidt, Joseph, additional, Johnson, Jeremy, additional, Cerrato, Felecia, additional, Petros, Brittany A, additional, Gionet, Gabi L, additional, Jalbert, Samantha K, additional, Cleary, Michael L, additional, Siddle, Katherine J, additional, Happi, Christain T, additional, Hung, Deborah T, additional, Springer, Michael, additional, MacInnis, Bronwyn, additional, Lemieux, Jacob, additional, Rosenberg, Eric S, additional, Branda, John A, additional, Blainey, Paul C, additional, Sabeti, Pardis, additional, and Myhrvold, Cameron, additional

Published
2021
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22. Random access DNA memory using Boolean search in an archival file storage system

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Banal, James L, Shepherd, Tyson R, Berleant, Joseph, Huang, Hellen, Reyes, Miguel, Ackerman, Cheri M, Blainey, Paul C, Bathe, Mark, Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Banal, James L, Shepherd, Tyson R, Berleant, Joseph, Huang, Hellen, Reyes, Miguel, Ackerman, Cheri M, Blainey, Paul C, and Bathe, Mark

Abstract

DNA is an ultrahigh-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and if random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. Here, we demonstrate a path to overcome the second barrier by encapsulating data-encoding DNA file sequences within impervious silica capsules that are surface labelled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling selection of sets of files with Boolean logic directly, without use of amplification. We demonstrate random access of image files from a prototypical 2-kilobyte image database using fluorescence sorting with selection sensitivity of one in 106 files, which thereby enables one in 106N selection capability using N optical channels. Our strategy thereby offers a scalable concept for random access of archival files in large-scale molecular datasets.

Published
2021

23. Arbitrary Boolean logical search operations on massive molecular file systems

Author

Banal, James L., Shepherd, Tyson R., Berleant, Joseph, Huang, Hellen, Reyes, Miguel, Ackerman, Cheri M., Blainey, Paul C., and Bathe, Mark

Abstract

DNA is an ultra-high-density storage medium that could meet exponentially growing worldwide data storage demand. However, accessing arbitrary data subsets within exabyte-scale DNA data pools is limited by the finite addressing space for individual DNA-based blocks of data. Here, we form files by encapsulating data-encoding DNA within silica capsules that are surface-labeled with multiple unique barcodes. Barcoding is performed with single-stranded DNA representing file metadata that enables Boolean logic selection on the entire pool of data. We demonstrate encapsulation and Boolean selection of sub-pools of image files using fluorescence-activated sorting, with selection sensitivity of 1 in 10 6 files per channel. Our strategy in principle enables retrieval of targeted data subsets from exabyte- and larger-scale data pools, thereby offering a random access file system for massive molecular data sets.

Published
2020
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24. Massively multiplexed nucleic acid detection using Cas13

Author

Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Ackerman, Cheri M., Myhrvold, Cameron, Thakku, Sri Gowtham, Freije, Catherine A., Metsky, Hayden C., Yang, David K., Ye, Simon H., Boehm, Chloe K., Kosoko-Thoroddsen, Tinna-Sólveig F., Kehe, Jared, Nguyen, Tien G., Carter, Amber, Kulesa, Anthony, Barnes, John R., Dugan, Vivien G., Hung, Deborah T., Blainey, Paul C., Sabeti, Pardis C., Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Ackerman, Cheri M., Myhrvold, Cameron, Thakku, Sri Gowtham, Freije, Catherine A., Metsky, Hayden C., Yang, David K., Ye, Simon H., Boehm, Chloe K., Kosoko-Thoroddsen, Tinna-Sólveig F., Kehe, Jared, Nguyen, Tien G., Carter, Amber, Kulesa, Anthony, Barnes, John R., Dugan, Vivien G., Hung, Deborah T., Blainey, Paul C., and Sabeti, Pardis C.

Abstract

The overwhelming majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples while simultaneously testing for many pathogens. Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanoliter droplets containing CRISPR-based nucleic acid detection reagents self-organize in a microwell array to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of >4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with ≥10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. CARMEN’s intrinsic multiplexing and throughput capabilities make it practical to scale, as miniaturization decreases reagent cost per test >300-fold. Scalable, highly-multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health. ©2020

Published
2020

25. Designing viral diagnostics with model-based optimization

Author

Metsky, Hayden C., primary, Welch, Nicole L., additional, Pillai, Priya P., additional, Haradhvala, Nicholas J., additional, Rumker, Laurie, additional, Mantena, Sreekar, additional, Zhang, Yibin B., additional, Yang, David K., additional, Ackerman, Cheri M., additional, Weller, Juliane, additional, Blainey, Paul C., additional, Myhrvold, Cameron, additional, Mitzenmacher, Michael, additional, and Sabeti, Pardis C., additional

Published
2020
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29. Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Author

Welch, Nicole L., Zhu, Meilin, Hua, Catherine, Weller, Juliane, Mirhashemi, Marzieh Ezzaty, Nguyen, Tien G., Mantena, Sreekar, Bauer, Matthew R., Shaw, Bennett M., Ackerman, Cheri M., Thakku, Sri Gowtham, Tse, Megan W., Kehe, Jared, Uwera, Marie-Martine, Eversley, Jacqueline S., Bielwaski, Derek A., McGrath, Graham, Braidt, Joseph, Johnson, Jeremy, Cerrato, Felecia, Moreno, Gage K., Krasilnikova, Lydia A., Petros, Brittany A., Gionet, Gabrielle L., King, Ewa, Huard, Richard C., Jalbert, Samantha K., Cleary, Michael L., Fitzgerald, Nicholas A., Gabriel, Stacey B., Gallagher, Glen R., Smole, Sandra C., Madoff, Lawrence C., Brown, Catherine M., Keller, Matthew W., Wilson, Malania M., Kirby, Marie K., Barnes, John R., Park, Daniel J., Siddle, Katherine J., Happi, Christian T., Hung, Deborah T., Springer, Michael, MacInnis, Bronwyn L., Lemieux, Jacob E., Rosenberg, Eric, Branda, John A., Blainey, Paul C., Sabeti, Pardis C., and Myhrvold, Cameron

Published
2024
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30. Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

Author

Leung, Wilson, primary, Shaffer, Christopher D, additional, Reed, Laura K, additional, Smith, Sheryl T, additional, Barshop, William, additional, Dirkes, William, additional, Dothager, Matthew, additional, Lee, Paul, additional, Wong, Jeannette, additional, Xiong, David, additional, Yuan, Han, additional, Bedard, James E J, additional, Machone, Joshua F, additional, Patterson, Seantay D, additional, Price, Amber L, additional, Turner, Bryce A, additional, Robic, Srebrenka, additional, Luippold, Erin K, additional, McCartha, Shannon R, additional, Walji, Tezin A, additional, Walker, Chelsea A, additional, Saville, Kenneth, additional, Abrams, Marita K, additional, Armstrong, Andrew R, additional, Armstrong, William, additional, Bailey, Robert J, additional, Barberi, Chelsea R, additional, Beck, Lauren R, additional, Blaker, Amanda L, additional, Blunden, Christopher E, additional, Brand, Jordan P, additional, Brock, Ethan J, additional, Brooks, Dana W, additional, Brown, Marie, additional, Butzler, Sarah C, additional, Clark, Eric M, additional, Clark, Nicole B, additional, Collins, Ashley A, additional, Cotteleer, Rebecca J, additional, Cullimore, Peterson R, additional, Dawson, Seth G, additional, Docking, Carter T, additional, Dorsett, Sasha L, additional, Dougherty, Grace A, additional, Downey, Kaitlyn A, additional, Drake, Andrew P, additional, Earl, Erica K, additional, Floyd, Trevor G, additional, Forsyth, Joshua D, additional, Foust, Jonathan D, additional, Franchi, Spencer L, additional, Geary, James F, additional, Hanson, Cynthia K, additional, Harding, Taylor S, additional, Harris, Cameron B, additional, Heckman, Jonathan M, additional, Holderness, Heather L, additional, Howey, Nicole A, additional, Jacobs, Dontae A, additional, Jewell, Elizabeth S, additional, Kaisler, Maria, additional, Karaska, Elizabeth A, additional, Kehoe, James L, additional, Koaches, Hannah C, additional, Koehler, Jessica, additional, Koenig, Dana, additional, Kujawski, Alexander J, additional, Kus, Jordan E, additional, Lammers, Jennifer A, additional, Leads, Rachel R, additional, Leatherman, Emily C, additional, Lippert, Rachel N, additional, Messenger, Gregory S, additional, Morrow, Adam T, additional, Newcomb, Victoria, additional, Plasman, Haley J, additional, Potocny, Stephanie J, additional, Powers, Michelle K, additional, Reem, Rachel M, additional, Rennhack, Jonathan P, additional, Reynolds, Katherine R, additional, Reynolds, Lyndsey A, additional, Rhee, Dong K, additional, Rivard, Allyson B, additional, Ronk, Adam J, additional, Rooney, Meghan B, additional, Rubin, Lainey S, additional, Salbert, Luke R, additional, Saluja, Rasleen K, additional, Schauder, Taylor, additional, Schneiter, Allison R, additional, Schulz, Robert W, additional, Smith, Karl E, additional, Spencer, Sarah, additional, Swanson, Bryant R, additional, Tache, Melissa A, additional, Tewilliager, Ashley A, additional, Tilot, Amanda K, additional, VanEck, Eve, additional, Villerot, Matthew M, additional, Vylonis, Megan B, additional, Watson, David T, additional, Wurzler, Juliana A, additional, Wysocki, Lauren M, additional, Yalamanchili, Monica, additional, Zaborowicz, Matthew A, additional, Emerson, Julia A, additional, Ortiz, Carlos, additional, Deuschle, Frederic J, additional, DiLorenzo, Lauren A, additional, Goeller, Katie L, additional, Macchi, Christopher R, additional, Muller, Sarah E, additional, Pasierb, Brittany D, additional, Sable, Joseph E, additional, Tucci, Jessica M, additional, Tynon, Marykathryn, additional, Dunbar, David A, additional, Beken, Levent H, additional, Conturso, Alaina C, additional, Danner, Benjamin L, additional, DeMichele, Gabriella A, additional, Gonzales, Justin A, additional, Hammond, Maureen S, additional, Kelley, Colleen V, additional, Kelly, Elisabeth A, additional, Kulich, Danielle, additional, Mageeney, Catherine M, additional, McCabe, Nikie L, additional, Newman, Alyssa M, additional, Spaeder, Lindsay A, additional, Tumminello, Richard A, additional, Revie, Dennis, additional, Benson, Jonathon M, additional, Cristostomo, Michael C, additional, DaSilva, Paolo A, additional, Harker, Katherine S, additional, Jarrell, Jenifer N, additional, Jimenez, Luis A, additional, Katz, Brandon M, additional, Kennedy, William R, additional, Kolibas, Kimberly S, additional, LeBlanc, Mark T, additional, Nguyen, Trung T, additional, Nicolas, Daniel S, additional, Patao, Melissa D, additional, Patao, Shane M, additional, Rupley, Bryan J, additional, Sessions, Bridget J, additional, Weaver, Jennifer A, additional, Goodman, Anya L, additional, Alvendia, Erica L, additional, Baldassari, Shana M, additional, Brown, Ashley S, additional, Chase, Ian O, additional, Chen, Maida, additional, Chiang, Scott, additional, Cromwell, Avery B, additional, Custer, Ashley F, additional, DiTommaso, Tia M, additional, El-Adaimi, Jad, additional, Goscinski, Nora C, additional, Grove, Ryan A, additional, Gutierrez, Nestor, additional, Harnoto, Raechel S, additional, Hedeen, Heather, additional, Hong, Emily L, additional, Hopkins, Barbara L, additional, Huerta, Vilma F, additional, Khoshabian, Colin, additional, LaForge, Kristin M, additional, Lee, Cassidy T, additional, Lewis, Benjamin M, additional, Lydon, Anniken M, additional, Maniaci, Brian J, additional, Mitchell, Ryan D, additional, Morlock, Elaine V, additional, Morris, William M, additional, Naik, Priyanka, additional, Olson, Nicole C, additional, Osterloh, Jeannette M, additional, Perez, Marcos A, additional, Presley, Jonathan D, additional, Randazzo, Matt J, additional, Regan, Melanie K, additional, Rossi, Franca G, additional, Smith, Melanie A, additional, Soliterman, Eugenia A, additional, Sparks, Ciani J, additional, Tran, Danny L, additional, Wan, Tiffany, additional, Welker, Anne A, additional, Wong, Jeremy N, additional, Sreenivasan, Aparna, additional, Youngblom, Jim, additional, Adams, Andrew, additional, Alldredge, Justin, additional, Bryant, Ashley, additional, Carranza, David, additional, Cifelli, Alyssa, additional, Coulson, Kevin, additional, Debow, Calise, additional, Delacruz, Noelle, additional, Emerson, Charlene, additional, Farrar, Cassandra, additional, Foret, Don, additional, Garibay, Edgar, additional, Gooch, John, additional, Heslop, Michelle, additional, Kaur, Sukhjit, additional, Khan, Ambreen, additional, Kim, Van, additional, Lamb, Travis, additional, Lindbeck, Peter, additional, Lucas, Gabi, additional, Macias, Elizabeth, additional, Martiniuc, Daniela, additional, Mayorga, Lissett, additional, Medina, Joseph, additional, Membreno, Nelson, additional, Messiah, Shady, additional, Neufeld, Lacey, additional, Nguyen, San Francisco, additional, Nichols, Zachary, additional, Odisho, George, additional, Peterson, Daymon, additional, Rodela, Laura, additional, Rodriguez, Priscilla, additional, Rodriguez, Vanessa, additional, Ruiz, Jorge, additional, Sherrill, Will, additional, Silva, Valeria, additional, Sparks, Jeri, additional, Statton, Geeta, additional, Townsend, Ashley, additional, Valdez, Isabel, additional, Waters, Mary, additional, Westphal, Kyle, additional, Winkler, Stacey, additional, Zumkehr, Joannee, additional, DeJong, Randall J, additional, Hoogewerf, Arlene J, additional, Ackerman, Cheri M, additional, Armistead, Isaac O, additional, Baatenburg, Lara, additional, Borr, Matthew J, additional, Brouwer, Lindsay K, additional, Burkhart, Brandon J, additional, Bushhouse, Kelsey T, additional, Cesko, Lejla, additional, Choi, Tiffany Y Y, additional, Cohen, Heather, additional, Damsteegt, Amanda M, additional, Darusz, Jess M, additional, Dauphin, Cory M, additional, Davis, Yelena P, additional, Diekema, Emily J, additional, Drewry, Melissa, additional, Eisen, Michelle E M, additional, Faber, Hayley M, additional, Faber, Katherine J, additional, Feenstra, Elizabeth, additional, Felzer-Kim, Isabella T, additional, Hammond, Brandy L, additional, Hendriksma, Jesse, additional, Herrold, Milton R, additional, Hilbrands, Julia A, additional, Howell, Emily J, additional, Jelgerhuis, Sarah A, additional, Jelsema, Timothy R, additional, Johnson, Benjamin K, additional, Jones, Kelly K, additional, Kim, Anna, additional, Kooienga, Ross D, additional, Menyes, Erika E, additional, Nollet, Eric A, additional, Plescher, Brittany E, additional, Rios, Lindsay, additional, Rose, Jenny L, additional, Schepers, Allison J, additional, Scott, Geoff, additional, Smith, Joshua R, additional, Sterling, Allison M, additional, Tenney, Jenna C, additional, Uitvlugt, Chris, additional, VanDyken, Rachel E, additional, VanderVennen, Marielle, additional, Vue, Samantha, additional, Kokan, Nighat P, additional, Agbley, Kwabea, additional, Boham, Sampson K, additional, Broomfield, Daniel, additional, Chapman, Kayla, additional, Dobbe, Ali, additional, Dobbe, Ian, additional, Harrington, William, additional, Ibrahem, Marwan, additional, Kennedy, Andre, additional, Koplinsky, Chad A, additional, Kubricky, Cassandra, additional, Ladzekpo, Danielle, additional, Pattison, Claire, additional, Ramirez, Roman E, additional, Wande, Lucia, additional, Woehlke, Sarah, additional, Wawersik, Matthew, additional, Kiernan, Elizabeth, additional, Thompson, Jeffrey S, additional, Banker, Roxanne, additional, Bartling, Justina R, additional, Bhatiya, Chinmoy I, additional, Boudoures, Anna L, additional, Christiansen, Lena, additional, Fosselman, Daniel S, additional, French, Kristin M, additional, Gill, Ishwar S, additional, Havill, Jessen T, additional, Johnson, Jaelyn L, additional, Keny, Lauren J, additional, Kerber, John M, additional, Klett, Bethany M, additional, Kufel, Christina N, additional, May, Francis J, additional, Mecoli, Jonathan P, additional, Merry, Callie R, additional, Meyer, Lauren R, additional, Miller, Emily G, additional, Mullen, Gregory J, additional, Palozola, Katherine C, additional, Pfeil, Jacob J, additional, Thomas, Jessica G, additional, Verbofsky, Evan M, additional, Spana, Eric P, additional, Agarwalla, Anant, additional, Chapman, Julia, additional, Chlebina, Ben, additional, Chong, Insun, additional, Falk, I N, additional, Fitzgibbons, John D, additional, Friedman, Harrison, additional, Ighile, Osagie, additional, Kim, Andrew J, additional, Knouse, Kristin A, additional, Kung, Faith, additional, Mammo, Danny, additional, Ng, Chun Leung, additional, Nikam, Vinayak S, additional, Norton, Diana, additional, Pham, Philip, additional, Polk, Jessica W, additional, Prasad, Shreya, additional, Rankin, Helen, additional, Ratliff, Camille D, additional, Scala, Victoria, additional, Schwartz, Nicholas U, additional, Shuen, Jessica A, additional, Xu, Amy, additional, Xu, Thomas Q, additional, Zhang, Yi, additional, Rosenwald, Anne G, additional, Burg, Martin G, additional, Adams, Stephanie J, additional, Baker, Morgan, additional, Botsford, Bobbi, additional, Brinkley, Briana, additional, Brown, Carter, additional, Emiah, Shadie, additional, Enoch, Erica, additional, Gier, Chad, additional, Greenwell, Alyson, additional, Hoogenboom, Lindsay, additional, Matthews, Jordan E, additional, McDonald, Mitchell, additional, Mercer, Amanda, additional, Monsma, Nicholaus, additional, Ostby, Kristine, additional, Ramic, Alen, additional, Shallman, Devon, additional, Simon, Matthew, additional, Spencer, Eric, additional, Tomkins, Trisha, additional, Wendland, Pete, additional, Wylie, Anna, additional, Wolyniak, Michael J, additional, Robertson, Gregory M, additional, Smith, Samuel I, additional, DiAngelo, Justin R, additional, Sassu, Eric D, additional, Bhalla, Satish C, additional, Sharif, Karim A, additional, Choeying, Tenzin, additional, Macias, Jason S, additional, Sanusi, Fareed, additional, Torchon, Karvyn, additional, Bednarski, April E, additional, Alvarez, Consuelo J, additional, Davis, Kristen C, additional, Dunham, Carrie A, additional, Grantham, Alaina J, additional, Hare, Amber N, additional, Schottler, Jennifer, additional, Scott, Zackary W, additional, Kuleck, Gary A, additional, Yu, Nicole S, additional, Kaehler, Marian M, additional, Jipp, Jacob, additional, Overvoorde, Paul J, additional, Shoop, Elizabeth, additional, Cyrankowski, Olivia, additional, Hoover, Betsy, additional, Kusner, Matt, additional, Lin, Devry, additional, Martinov, Tijana, additional, Misch, Jonathan, additional, Salzman, Garrett, additional, Schiedermayer, Holly, additional, Snavely, Michael, additional, Zarrasola, Stephanie, additional, Parrish, Susan, additional, Baker, Atlee, additional, Beckett, Alissa, additional, Belella, Carissa, additional, Bryant, Julie, additional, Conrad, Turner, additional, Fearnow, Adam, additional, Gomez, Carolina, additional, Herbstsomer, Robert A, additional, Hirsch, Sarah, additional, Johnson, Christen, additional, Jones, Melissa, additional, Kabaso, Rita, additional, Lemmon, Eric, additional, Vieira, Carolina Marques dos Santos, additional, McFarland, Darryl, additional, McLaughlin, Christopher, additional, Morgan, Abbie, additional, Musokotwane, Sepo, additional, Neutzling, William, additional, Nietmann, Jana, additional, Paluskievicz, Christina, additional, Penn, Jessica, additional, Peoples, Emily, additional, Pozmanter, Caitlin, additional, Reed, Emily, additional, Rigby, Nichole, additional, Schmidt, Lasse, additional, Shelton, Micah, additional, Shuford, Rebecca, additional, Tirasawasdichai, Tiara, additional, Undem, Blair, additional, Urick, Damian, additional, Vondy, Kayla, additional, Yarrington, Bryan, additional, Eckdahl, Todd T, additional, Poet, Jeffrey L, additional, Allen, Alica B, additional, Anderson, John E, additional, Barnett, Jason M, additional, Baumgardner, Jordan S, additional, Brown, Adam D, additional, Carney, Jordan E, additional, Chavez, Ramiro A, additional, Christgen, Shelbi L, additional, Christie, Jordan S, additional, Clary, Andrea N, additional, Conn, Michel A, additional, Cooper, Kristen M, additional, Crowley, Matt J, additional, Crowley, Samuel T, additional, Doty, Jennifer S, additional, Dow, Brian A, additional, Edwards, Curtis R, additional, Elder, Darcie D, additional, Fanning, John P, additional, Janssen, Bridget M, additional, Lambright, Anthony K, additional, Lane, Curtiss E, additional, Limle, Austin B, additional, Mazur, Tammy, additional, McCracken, Marly R, additional, McDonough, Alexa M, additional, Melton, Amy D, additional, Minnick, Phillip J, additional, Musick, Adam E, additional, Newhart, William H, additional, Noynaert, Joseph W, additional, Ogden, Bradley J, additional, Sandusky, Michael W, additional, Schmuecker, Samantha M, additional, Shipman, Anna L, additional, Smith, Anna L, additional, Thomsen, Kristen M, additional, Unzicker, Matthew R, additional, Vernon, William B, additional, Winn, Wesley W, additional, Woyski, Dustin S, additional, Zhu, Xiao, additional, Du, Chunguang, additional, Ament, Caitlin, additional, Aso, Soham, additional, Bisogno, Laura Simone, additional, Caronna, Jason, additional, Fefelova, Nadezhda, additional, Lopez, Lenin, additional, Malkowitz, Lorraine, additional, Marra, Jonathan, additional, Menillo, Daniella, additional, Obiorah, Ifeanyi, additional, Onsarigo, Eric Nyabeta, additional, Primus, Shekerah, additional, Soos, Mahdi, additional, Tare, Archana, additional, Zidan, Ameer, additional, Jones, Christopher J, additional, Aronhalt, Todd, additional, Bellush, James M, additional, Burke, Christa, additional, DeFazio, Steve, additional, Does, Benjamin R, additional, Johnson, Todd D, additional, Keysock, Nicholas, additional, Knudsen, Nelson H, additional, Messler, James, additional, Myirski, Kevin, additional, Rekai, Jade Lea, additional, Rempe, Ryan Michael, additional, Salgado, Michael S, additional, Stagaard, Erica, additional, Starcher, Justin R, additional, Waggoner, Andrew W, additional, Yemelyanova, Anastasia K, additional, Hark, Amy T, additional, Bertolet, Anne, additional, Kuschner, Cyrus E, additional, Parry, Kesley, additional, Quach, Michael, additional, Shantzer, Lindsey, additional, Shaw, Mary E, additional, Smith, Mary A, additional, Glenn, Omolara, additional, Mason, Portia, additional, Williams, Charlotte, additional, Key, S Catherine Silver, additional, Henry, Tyneshia C P, additional, Johnson, Ashlee G, additional, White, Jackie X, additional, Haberman, Adam, additional, Asinof, Sam, additional, Drumm, Kelly, additional, Freeburg, Trip, additional, Safa, Nadia, additional, Schultz, Darrin, additional, Shevin, Yakov, additional, Svoronos, Petros, additional, Vuong, Tam, additional, Wellinghoff, Jules, additional, Hoopes, Laura L M, additional, Chau, Kim M, additional, Ward, Alyssa, additional, Regisford, E Gloria C, additional, Augustine, LaJerald, additional, Davis-Reyes, Brionna, additional, Echendu, Vivienne, additional, Hales, Jasmine, additional, Ibarra, Sharon, additional, Johnson, Lauriaun, additional, Ovu, Steven, additional, Braverman, John M, additional, Bahr, Thomas J, additional, Caesar, Nicole M, additional, Campana, Christopher, additional, Cassidy, Daniel W, additional, Cognetti, Peter A, additional, English, Johnathan D, additional, Fadus, Matthew C, additional, Fick, Cameron N, additional, Freda, Philip J, additional, Hennessy, Bryan M, additional, Hockenberger, Kelsey, additional, Jones, Jennifer K, additional, King, Jessica E, additional, Knob, Christopher R, additional, Kraftmann, Karen J, additional, Li, Linghui, additional, Lupey, Lena N, additional, Minniti, Carl J, additional, Minton, Thomas F, additional, Moran, Joseph V, additional, Mudumbi, Krishna, additional, Nordman, Elizabeth C, additional, Puetz, William J, additional, Robinson, Lauren M, additional, Rose, Thomas J, additional, Sweeney, Edward P, additional, Timko, Ashley S, additional, Paetkau, Don W, additional, Eisler, Heather L, additional, Aldrup, Megan E, additional, Bodenberg, Jessica M, additional, Cole, Mara G, additional, Deranek, Kelly M, additional, DeShetler, Megan, additional, Dowd, Rose M, additional, Eckardt, Alexandra K, additional, Ehret, Sharon C, additional, Fese, Jessica, additional, Garrett, Amanda D, additional, Kammrath, Anna, additional, Kappes, Michelle L, additional, Light, Morgan R, additional, Meier, Anne C, additional, O’Rouke, Allison, additional, Perella, Mallory, additional, Ramsey, Kimberley, additional, Ramthun, Jennifer R, additional, Reilly, Mary T, additional, Robinett, Deirdre, additional, Rossi, Nadine L, additional, Schueler, Mary Grace, additional, Shoemaker, Emma, additional, Starkey, Kristin M, additional, Vetor, Ashley, additional, Vrable, Abby, additional, Chandrasekaran, Vidya, additional, Beck, Christopher, additional, Hatfield, Kristen R, additional, Herrick, Douglas A, additional, Khoury, Christopher B, additional, Lea, Charlotte, additional, Louie, Christopher A, additional, Lowell, Shannon M, additional, Reynolds, Thomas J, additional, Schibler, Jeanine, additional, Scoma, Alexandra H, additional, Smith-Gee, Maxwell T, additional, Tuberty, Sarah, additional, Smith, Christopher D, additional, Lopilato, Jane E, additional, Hauke, Jeanette, additional, Roecklein-Canfield, Jennifer A, additional, Corrielus, Maureen, additional, Gilman, Hannah, additional, Intriago, Stephanie, additional, Maffa, Amanda, additional, Rauf, Sabya A, additional, Thistle, Katrina, additional, Trieu, Melissa, additional, Winters, Jenifer, additional, Yang, Bib, additional, Hauser, Charles R, additional, Abusheikh, Tariq, additional, Ashrawi, Yara, additional, Benitez, Pedro, additional, Boudreaux, Lauren R, additional, Bourland, Megan, additional, Chavez, Miranda, additional, Cruz, Samantha, additional, Elliott, GiNell, additional, Farek, Jesse R, additional, Flohr, Sarah, additional, Flores, Amanda H, additional, Friedrichs, Chelsey, additional, Fusco, Zach, additional, Goodwin, Zane, additional, Helmreich, Eric, additional, Kiley, John, additional, Knepper, John Mark, additional, Langner, Christine, additional, Martinez, Megan, additional, Mendoza, Carlos, additional, Naik, Monal, additional, Ochoa, Andrea, additional, Ragland, Nicolas, additional, Raimey, England, additional, Rathore, Sunil, additional, Reza, Evangelina, additional, Sadovsky, Griffin, additional, Seydoux, Marie-Isabelle B, additional, Smith, Jonathan E, additional, Unruh, Anna K, additional, Velasquez, Vicente, additional, Wolski, Matthew W, additional, Gosser, Yuying, additional, Govind, Shubha, additional, Clarke-Medley, Nicole, additional, Guadron, Leslie, additional, Lau, Dawn, additional, Lu, Alvin, additional, Mazzeo, Cheryl, additional, Meghdari, Mariam, additional, Ng, Simon, additional, Pamnani, Brad, additional, Plante, Olivia, additional, Shum, Yuki Kwan Wa, additional, Song, Roy, additional, Johnson, Diana E, additional, Abdelnabi, Mai, additional, Archambault, Alexi, additional, Chamma, Norma, additional, Gaur, Shailly, additional, Hammett, Deborah, additional, Kandahari, Adrese, additional, Khayrullina, Guzal, additional, Kumar, Sonali, additional, Lawrence, Samantha, additional, Madden, Nigel, additional, Mandelbaum, Max, additional, Milnthorp, Heather, additional, Mohini, Shiv, additional, Patel, Roshni, additional, Peacock, Sarah J, additional, Perling, Emily, additional, Quintana, Amber, additional, Rahimi, Michael, additional, Ramirez, Kristen, additional, Singhal, Rishi, additional, Weeks, Corinne, additional, Wong, Tiffany, additional, Gillis, Aubree T, additional, Moore, Zachary D, additional, Savell, Christopher D, additional, Watson, Reece, additional, Mel, Stephanie F, additional, Anilkumar, Arjun A, additional, Bilinski, Paul, additional, Castillo, Rostislav, additional, Closser, Michael, additional, Cruz, Nathalia M, additional, Dai, Tiffany, additional, Garbagnati, Giancarlo F, additional, Horton, Lanor S, additional, Kim, Dongyeon, additional, Lau, Joyce H, additional, Liu, James Z, additional, Mach, Sandy D, additional, Phan, Thu A, additional, Ren, Yi, additional, Stapleton, Kenneth E, additional, Strelitz, Jean M, additional, Sunjed, Ray, additional, Stamm, Joyce, additional, Anderson, Morgan C, additional, Bonifield, Bethany Grace, additional, Coomes, Daniel, additional, Dillman, Adam, additional, Durchholz, Elaine J, additional, Fafara-Thompson, Antoinette E, additional, Gross, Meleah J, additional, Gygi, Amber M, additional, Jackson, Lesley E, additional, Johnson, Amy, additional, Kocsisova, Zuzana, additional, Manghelli, Joshua L, additional, McNeil, Kylie, additional, Murillo, Michael, additional, Naylor, Kierstin L, additional, Neely, Jessica, additional, Ogawa, Emmy E, additional, Rich, Ashley, additional, Rogers, Anna, additional, Spencer, J Devin, additional, Stemler, Kristina M, additional, Throm, Allison A, additional, Van Camp, Matt, additional, Weihbrecht, Katie, additional, Wiles, T Aaron, additional, Williams, Mallory A, additional, Williams, Matthew, additional, Zoll, Kyle, additional, Bailey, Cheryl, additional, Zhou, Leming, additional, Balthaser, Darla M, additional, Bashiri, Azita, additional, Bower, Mindy E, additional, Florian, Kayla A, additional, Ghavam, Nazanin, additional, Greiner-Sosanko, Elizabeth S, additional, Karim, Helmet, additional, Mullen, Victor W, additional, Pelchen, Carly E, additional, Yenerall, Paul M, additional, Zhang, Jiayu, additional, Rubin, Michael R, additional, Arias-Mejias, Suzette M, additional, Bermudez-Capo, Armando G, additional, Bernal-Vega, Gabriela V, additional, Colon-Vazquez, Mariela, additional, Flores-Vazquez, Arelys, additional, Gines-Rosario, Mariela, additional, Llavona-Cartagena, Ivan G, additional, Martinez-Rodriguez, Javier O, additional, Ortiz-Fuentes, Lionel, additional, Perez-Colomba, Eliezer O, additional, Perez-Otero, Joseph, additional, Rivera, Elisandra, additional, Rodriguez-Giron, Luke J, additional, Santiago-Sanabria, Arnaldo J, additional, Senquiz-Gonzalez, Andrea M, additional, delValle, Frank R Soto, additional, Vargas-Franco, Dorianmarie, additional, Velázquez-Soto, Karla I, additional, Zambrana-Burgos, Joan D, additional, Martinez-Cruzado, Juan Carlos, additional, Asencio-Zayas, Lillyann, additional, Babilonia-Figueroa, Kevin, additional, Beauchamp-Pérez, Francis D, additional, Belén-Rodríguez, Juliana, additional, Bracero-Quiñones, Luciann, additional, Burgos-Bula, Andrea P, additional, Collado-Méndez, Xavier A, additional, Colón-Cruz, Luis R, additional, Correa-Muller, Ana I, additional, Crooke-Rosado, Jonathan L, additional, Cruz-García, José M, additional, Defendini-Ávila, Marianna, additional, Delgado-Peraza, Francheska M, additional, Feliciano-Cancela, Alex J, additional, Gónzalez-Pérez, Valerie M, additional, Guiblet, Wilfried, additional, Heredia-Negrón, Aldo, additional, Hernández-Muñiz, Jennifer, additional, Irizarry-González, Lourdes N, additional, Laboy-Corales, Ángel L, additional, Llaurador-Caraballo, Gabriela A, additional, Marín-Maldonado, Frances, additional, Marrero-Llerena, Ulises, additional, Martell-Martínez, Héctor A, additional, Martínez-Traverso, Idaliz M, additional, Medina-Ortega, Kiara N, additional, Méndez-Castellanos, Sonya G, additional, Menéndez-Serrano, Krizia C, additional, Morales-Caraballo, Carol I, additional, Ortiz-DeChoudens, Saryleine, additional, Ortiz-Ortiz, Patricia, additional, Pagán-Torres, Hendrick, additional, Pérez-Afanador, Diana, additional, Quintana-Torres, Enid M, additional, Ramírez-Aponte, Edwin G, additional, Riascos-Cuero, Carolina, additional, Rivera-Llovet, Michelle S, additional, Rivera-Pagán, Ingrid T, additional, Rivera-Vicéns, Ramón E, additional, Robles-Juarbe, Fabiola, additional, Rodríguez-Bonilla, Lorraine, additional, Rodríguez-Echevarría, Brian O, additional, Rodríguez-García, Priscila M, additional, Rodríguez-Laboy, Abneris E, additional, Rodríguez-Santiago, Susana, additional, Rojas-Vargas, Michael L, additional, Rubio-Marrero, Eva N, additional, Santiago-Colón, Albeliz, additional, Santiago-Ortiz, Jorge L, additional, Santos-Ramos, Carlos E, additional, Serrano-González, Joseline, additional, Tamayo-Figueroa, Alina M, additional, Tascón-Peñaranda, Edna P, additional, Torres-Castillo, José L, additional, Valentín-Feliciano, Nelson A, additional, Valentín-Feliciano, Yashira M, additional, Vargas-Barreto, Nadyan M, additional, Vélez-Vázquez, Miguel, additional, Vilanova-Vélez, Luis R, additional, Zambrana-Echevarría, Cristina, additional, MacKinnon, Christy, additional, Chung, Hui-Min, additional, Kay, Chris, additional, Pinto, Anthony, additional, Kopp, Olga R, additional, Burkhardt, Joshua, additional, Harward, Chris, additional, Allen, Robert, additional, Bhat, Pavan, additional, Chang, Jimmy Hsiang-Chun, additional, Chen, York, additional, Chesley, Christopher, additional, Cohn, Dara, additional, DuPuis, David, additional, Fasano, Michael, additional, Fazzio, Nicholas, additional, Gavinski, Katherine, additional, Gebreyesus, Heran, additional, Giarla, Thomas, additional, Gostelow, Marcus, additional, Greenstein, Rachel, additional, Gunasinghe, Hashini, additional, Hanson, Casey, additional, Hay, Amanda, additional, He, Tao Jian, additional, Homa, Katie, additional, Howe, Ruth, additional, Howenstein, Jeff, additional, Huang, Henry, additional, Khatri, Aaditya, additional, Kim, Young Lu, additional, Knowles, Olivia, additional, Kong, Sarah, additional, Krock, Rebecca, additional, Kroll, Matt, additional, Kuhn, Julia, additional, Kwong, Matthew, additional, Lee, Brandon, additional, Lee, Ryan, additional, Levine, Kevin, additional, Li, Yedda, additional, Liu, Bo, additional, Liu, Lucy, additional, Liu, Max, additional, Lousararian, Adam, additional, Ma, Jimmy, additional, Mallya, Allyson, additional, Manchee, Charlie, additional, Marcus, Joseph, additional, McDaniel, Stephen, additional, Miller, Michelle L, additional, Molleston, Jerome M, additional, Diez, Cristina Montero, additional, Ng, Patrick, additional, Ngai, Natalie, additional, Nguyen, Hien, additional, Nylander, Andrew, additional, Pollack, Jason, additional, Rastogi, Suchita, additional, Reddy, Himabindu, additional, Regenold, Nathaniel, additional, Sarezky, Jon, additional, Schultz, Michael, additional, Shim, Jien, additional, Skorupa, Tara, additional, Smith, Kenneth, additional, Spencer, Sarah J, additional, Srikanth, Priya, additional, Stancu, Gabriel, additional, Stein, Andrew P, additional, Strother, Marshall, additional, Sudmeier, Lisa, additional, Sun, Mengyang, additional, Sundaram, Varun, additional, Tazudeen, Noor, additional, Tseng, Alan, additional, Tzeng, Albert, additional, Venkat, Rohit, additional, Venkataram, Sandeep, additional, Waldman, Leah, additional, Wang, Tracy, additional, Yang, Hao, additional, Yu, Jack Y, additional, Zheng, Yin, additional, Preuss, Mary L, additional, Garcia, Angelica, additional, Juergens, Matt, additional, Morris, Robert W, additional, Nagengast, Alexis A, additional, Azarewicz, Julie, additional, Carr, Thomas J, additional, Chichearo, Nicole, additional, Colgan, Mike, additional, Donegan, Megan, additional, Gardner, Bob, additional, Kolba, Nik, additional, Krumm, Janice L, additional, Lytle, Stacey, additional, MacMillian, Laurell, additional, Miller, Mary, additional, Montgomery, Andrew, additional, Moretti, Alysha, additional, Offenbacker, Brittney, additional, Polen, Mike, additional, Toth, John, additional, Woytanowski, John, additional, Kadlec, Lisa, additional, Crawford, Justin, additional, Spratt, Mary L, additional, Adams, Ashley L, additional, Barnard, Brianna K, additional, Cheramie, Martin N, additional, Eime, Anne M, additional, Golden, Kathryn L, additional, Hawkins, Allyson P, additional, Hill, Jessica E, additional, Kampmeier, Jessica A, additional, Kern, Cody D, additional, Magnuson, Emily E, additional, Miller, Ashley R, additional, Morrow, Cody M, additional, Peairs, Julia C, additional, Pickett, Gentry L, additional, Popelka, Sarah A, additional, Scott, Alexis J, additional, Teepe, Emily J, additional, TerMeer, Katie A, additional, Watchinski, Carmen A, additional, Watson, Lucas A, additional, Weber, Rachel E, additional, Woodard, Kate A, additional, Barnard, Daron C, additional, Appiah, Isaac, additional, Giddens, Michelle M, additional, McNeil, Gerard P, additional, Adebayo, Adeola, additional, Bagaeva, Kate, additional, Chinwong, Justina, additional, Dol, Chrystel, additional, George, Eunice, additional, Haltaufderhyde, Kirk, additional, Haye, Joanna, additional, Kaur, Manpreet, additional, Semon, Max, additional, Serjanov, Dmitri, additional, Toorie, Anika, additional, Wilson, Christopher, additional, Riddle, Nicole C, additional, Buhler, Jeremy, additional, Mardis, Elaine R, additional, and Elgin, Sarah C R, additional

Published
2015
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33. Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

Author

Leung W, Shaffer CD, Reed LK, Smith ST, Barshop W, Dirkes W, Dothager M, Lee P, Wong J, Xiong D, Yuan H, Bedard JE, Machone JF, Patterson SD, Price AL, Turner BA, Robic S, Luippold EK, McCartha SR, Walji TA, Walker CA, Saville K, Abrams MK, Armstrong AR, Armstrong W, Bailey RJ, Barberi CR, Beck LR, Blaker AL, Blunden CE, Brand JP, Brock EJ, Brooks DW, Brown M, Butzler SC, Clark EM, Clark NB, Collins AA, Cotteleer RJ, Cullimore PR, Dawson SG, Docking CT, Dorsett SL, Dougherty GA, Downey KA, Drake AP, Earl EK, Floyd TG, Forsyth JD, Foust JD, Franchi SL, Geary JF, Hanson CK, Harding TS, Harris CB, Heckman JM, Holderness HL, Howey NA, Jacobs DA, Jewell ES, Kaisler M, Karaska EA, Kehoe JL, Koaches HC, Koehler J, Koenig D, Kujawski AJ, Kus JE, Lammers JA, Leads RR, Leatherman EC, Lippert RN, Messenger GS, Morrow AT, Newcomb V, Plasman HJ, Potocny SJ, Powers MK, Reem RM, Rennhack JP, Reynolds KR, Reynolds LA, Rhee DK, Rivard AB, Ronk AJ, Rooney MB, Rubin LS, Salbert LR, Saluja RK, Schauder T, Schneiter AR, Schulz RW, Smith KE, Spencer S, Swanson BR, Tache MA, Tewilliager AA, Tilot AK, VanEck E, Villerot MM, Vylonis MB, Watson DT, Wurzler JA, Wysocki LM, Yalamanchili M, Zaborowicz MA, Emerson JA, Ortiz C, Deuschle FJ, DiLorenzo LA, Goeller KL, Macchi CR, Muller SE, Pasierb BD, Sable JE, Tucci JM, Tynon M, Dunbar DA, Beken LH, Conturso AC, Danner BL, DeMichele GA, Gonzales JA, Hammond MS, Kelley CV, Kelly EA, Kulich D, Mageeney CM, McCabe NL, Newman AM, Spaeder LA, Tumminello RA, Revie D, Benson JM, Cristostomo MC, DaSilva PA, Harker KS, Jarrell JN, Jimenez LA, Katz BM, Kennedy WR, Kolibas KS, LeBlanc MT, Nguyen TT, Nicolas DS, Patao MD, Patao SM, Rupley BJ, Sessions BJ, Weaver JA, Goodman AL, Alvendia EL, Baldassari SM, Brown AS, Chase IO, Chen M, Chiang S, Cromwell AB, Custer AF, DiTommaso TM, El-Adaimi J, Goscinski NC, Grove RA, Gutierrez N, Harnoto RS, Hedeen H, Hong EL, Hopkins BL, Huerta VF, Khoshabian C, LaForge KM, Lee CT, Lewis BM, Lydon AM, Maniaci BJ, Mitchell RD, Morlock EV, Morris WM, Naik P, Olson NC, Osterloh JM, Perez MA, Presley JD, Randazzo MJ, Regan MK, Rossi FG, Smith MA, Soliterman EA, Sparks CJ, Tran DL, Wan T, Welker AA, Wong JN, Sreenivasan A, Youngblom J, Adams A, Alldredge J, Bryant A, Carranza D, Cifelli A, Coulson K, Debow C, Delacruz N, Emerson C, Farrar C, Foret D, Garibay E, Gooch J, Heslop M, Kaur S, Khan A, Kim V, Lamb T, Lindbeck P, Lucas G, Macias E, Martiniuc D, Mayorga L, Medina J, Membreno N, Messiah S, Neufeld L, Nguyen SF, Nichols Z, Odisho G, Peterson D, Rodela L, Rodriguez P, Rodriguez V, Ruiz J, Sherrill W, Silva V, Sparks J, Statton G, Townsend A, Valdez I, Waters M, Westphal K, Winkler S, Zumkehr J, DeJong RJ, Hoogewerf AJ, Ackerman CM, Armistead IO, Baatenburg L, Borr MJ, Brouwer LK, Burkhart BJ, Bushhouse KT, Cesko L, Choi TY, Cohen H, Damsteegt AM, Darusz JM, Dauphin CM, Davis YP, Diekema EJ, Drewry M, Eisen ME, Faber HM, Faber KJ, Feenstra E, Felzer-Kim IT, Hammond BL, Hendriksma J, Herrold MR, Hilbrands JA, Howell EJ, Jelgerhuis SA, Jelsema TR, Johnson BK, Jones KK, Kim A, Kooienga RD, Menyes EE, Nollet EA, Plescher BE, Rios L, Rose JL, Schepers AJ, Scott G, Smith JR, Sterling AM, Tenney JC, Uitvlugt C, VanDyken RE, VanderVennen M, Vue S, Kokan NP, Agbley K, Boham SK, Broomfield D, Chapman K, Dobbe A, Dobbe I, Harrington W, Ibrahem M, Kennedy A, Koplinsky CA, Kubricky C, Ladzekpo D, Pattison C, Ramirez RE Jr, Wande L, Woehlke S, Wawersik M, Kiernan E, Thompson JS, Banker R, Bartling JR, Bhatiya CI, Boudoures AL, Christiansen L, Fosselman DS, French KM, Gill IS, Havill JT, Johnson JL, Keny LJ, Kerber JM, Klett BM, Kufel CN, May FJ, Mecoli JP, Merry CR, Meyer LR, Miller EG, Mullen GJ, Palozola KC, Pfeil JJ, Thomas JG, Verbofsky EM, Spana EP, Agarwalla A, Chapman J, Chlebina B, Chong I, Falk IN, Fitzgibbons JD, Friedman H, Ighile O, Kim AJ, Knouse KA, Kung F, Mammo D, Ng CL, Nikam VS, Norton D, Pham P, Polk JW, Prasad S, Rankin H, Ratliff CD, Scala V, Schwartz NU, Shuen JA, Xu A, Xu TQ, Zhang Y, Rosenwald AG, Burg MG, Adams SJ, Baker M, Botsford B, Brinkley B, Brown C, Emiah S, Enoch E, Gier C, Greenwell A, Hoogenboom L, Matthews JE, McDonald M, Mercer A, Monsma N, Ostby K, Ramic A, Shallman D, Simon M, Spencer E, Tomkins T, Wendland P, Wylie A, Wolyniak MJ, Robertson GM, Smith SI, DiAngelo JR, Sassu ED, Bhalla SC, Sharif KA, Choeying T, Macias JS, Sanusi F, Torchon K, Bednarski AE, Alvarez CJ, Davis KC, Dunham CA, Grantham AJ, Hare AN, Schottler J, Scott ZW, Kuleck GA, Yu NS, Kaehler MM, Jipp J, Overvoorde PJ, Shoop E, Cyrankowski O, Hoover B, Kusner M, Lin D, Martinov T, Misch J, Salzman G, Schiedermayer H, Snavely M, Zarrasola S, Parrish S, Baker A, Beckett A, Belella C, Bryant J, Conrad T, Fearnow A, Gomez C, Herbstsomer RA, Hirsch S, Johnson C, Jones M, Kabaso R, Lemmon E, Vieira CM, McFarland D, McLaughlin C, Morgan A, Musokotwane S, Neutzling W, Nietmann J, Paluskievicz C, Penn J, Peoples E, Pozmanter C, Reed E, Rigby N, Schmidt L, Shelton M, Shuford R, Tirasawasdichai T, Undem B, Urick D, Vondy K, Yarrington B, Eckdahl TT, Poet JL, Allen AB, Anderson JE, Barnett JM, Baumgardner JS, Brown AD, Carney JE, Chavez RA, Christgen SL, Christie JS, Clary AN, Conn MA, Cooper KM, Crowley MJ, Crowley ST, Doty JS, Dow BA, Edwards CR, Elder DD, Fanning JP, Janssen BM, Lambright AK, Lane CE, Limle AB, Mazur T, McCracken MR, McDonough AM, Melton AD, Minnick PJ, Musick AE, Newhart WH, Noynaert JW, Ogden BJ, Sandusky MW, Schmuecker SM, Shipman AL, Smith AL, Thomsen KM, Unzicker MR, Vernon WB, Winn WW, Woyski DS, Zhu X, Du C, Ament C, Aso S, Bisogno LS, Caronna J, Fefelova N, Lopez L, Malkowitz L, Marra J, Menillo D, Obiorah I, Onsarigo EN, Primus S, Soos M, Tare A, Zidan A, Jones CJ, Aronhalt T, Bellush JM, Burke C, DeFazio S, Does BR, Johnson TD, Keysock N, Knudsen NH, Messler J, Myirski K, Rekai JL, Rempe RM, Salgado MS, Stagaard E, Starcher JR, Waggoner AW, Yemelyanova AK, Hark AT, Bertolet A, Kuschner CE, Parry K, Quach M, Shantzer L, Shaw ME, Smith MA, Glenn O, Mason P, Williams C, Key SC, Henry TC, Johnson AG, White JX, Haberman A, Asinof S, Drumm K, Freeburg T, Safa N, Schultz D, Shevin Y, Svoronos P, Vuong T, Wellinghoff J, Hoopes LL, Chau KM, Ward A, Regisford EG, Augustine L, Davis-Reyes B, Echendu V, Hales J, Ibarra S, Johnson L, Ovu S, Braverman JM, Bahr TJ, Caesar NM, Campana C, Cassidy DW, Cognetti PA, English JD, Fadus MC, Fick CN, Freda PJ, Hennessy BM, Hockenberger K, Jones JK, King JE, Knob CR, Kraftmann KJ, Li L, Lupey LN, Minniti CJ, Minton TF, Moran JV, Mudumbi K, Nordman EC, Puetz WJ, Robinson LM, Rose TJ, Sweeney EP, Timko AS, Paetkau DW, Eisler HL, Aldrup ME, Bodenberg JM, Cole MG, Deranek KM, DeShetler M, Dowd RM, Eckardt AK, Ehret SC, Fese J, Garrett AD, Kammrath A, Kappes ML, Light MR, Meier AC, O'Rouke A, Perella M, Ramsey K, Ramthun JR, Reilly MT, Robinett D, Rossi NL, Schueler MG, Shoemaker E, Starkey KM, Vetor A, Vrable A, Chandrasekaran V, Beck C, Hatfield KR, Herrick DA, Khoury CB, Lea C, Louie CA, Lowell SM, Reynolds TJ, Schibler J, Scoma AH, Smith-Gee MT, Tuberty S, Smith CD, Lopilato JE, Hauke J, Roecklein-Canfield JA, Corrielus M, Gilman H, Intriago S, Maffa A, Rauf SA, Thistle K, Trieu M, Winters J, Yang B, Hauser CR, Abusheikh T, Ashrawi Y, Benitez P, Boudreaux LR, Bourland M, Chavez M, Cruz S, Elliott G, Farek JR, Flohr S, Flores AH, Friedrichs C, Fusco Z, Goodwin Z, Helmreich E, Kiley J, Knepper JM, Langner C, Martinez M, Mendoza C, Naik M, Ochoa A, Ragland N, Raimey E, Rathore S, Reza E, Sadovsky G, Seydoux MI, Smith JE, Unruh AK, Velasquez V, Wolski MW, Gosser Y, Govind S, Clarke-Medley N, Guadron L, Lau D, Lu A, Mazzeo C, Meghdari M, Ng S, Pamnani B, Plante O, Shum YK, Song R, Johnson DE, Abdelnabi M, Archambault A, Chamma N, Gaur S, Hammett D, Kandahari A, Khayrullina G, Kumar S, Lawrence S, Madden N, Mandelbaum M, Milnthorp H, Mohini S, Patel R, Peacock SJ, Perling E, Quintana A, Rahimi M, Ramirez K, Singhal R, Weeks C, Wong T, Gillis AT, Moore ZD, Savell CD, Watson R, Mel SF, Anilkumar AA, Bilinski P, Castillo R, Closser M, Cruz NM, Dai T, Garbagnati GF, Horton LS, Kim D, Lau JH, Liu JZ, Mach SD, Phan TA, Ren Y, Stapleton KE, Strelitz JM, Sunjed R, Stamm J, Anderson MC, Bonifield BG, Coomes D, Dillman A, Durchholz EJ, Fafara-Thompson AE, Gross MJ, Gygi AM, Jackson LE, Johnson A, Kocsisova Z, Manghelli JL, McNeil K, Murillo M, Naylor KL, Neely J, Ogawa EE, Rich A, Rogers A, Spencer JD, Stemler KM, Throm AA, Van Camp M, Weihbrecht K, Wiles TA, Williams MA, Williams M, Zoll K, Bailey C, Zhou L, Balthaser DM, Bashiri A, Bower ME, Florian KA, Ghavam N, Greiner-Sosanko ES, Karim H, Mullen VW, Pelchen CE, Yenerall PM, Zhang J, Rubin MR, Arias-Mejias SM, Bermudez-Capo AG, Bernal-Vega GV, Colon-Vazquez M, Flores-Vazquez A, Gines-Rosario M, Llavona-Cartagena IG, Martinez-Rodriguez JO, Ortiz-Fuentes L, Perez-Colomba EO, Perez-Otero J, Rivera E, Rodriguez-Giron LJ, Santiago-Sanabria AJ, Senquiz-Gonzalez AM, delValle FR, Vargas-Franco D, Velázquez-Soto KI, Zambrana-Burgos JD, Martinez-Cruzado JC, Asencio-Zayas L, Babilonia-Figueroa K, Beauchamp-Pérez FD, Belén-Rodríguez J, Bracero-Quiñones L, Burgos-Bula AP, Collado-Méndez XA, Colón-Cruz LR, Correa-Muller AI, Crooke-Rosado JL, Cruz-García JM, Defendini-Ávila M, Delgado-Peraza FM, Feliciano-Cancela AJ, Gónzalez-Pérez VM, Guiblet W, Heredia-Negrón A, Hernández-Muñiz J, Irizarry-González LN, Laboy-Corales ÁL, Llaurador-Caraballo GA, Marín-Maldonado F, Marrero-Llerena U, Martell-Martínez HA, Martínez-Traverso IM, Medina-Ortega KN, Méndez-Castellanos SG, Menéndez-Serrano KC, Morales-Caraballo CI, Ortiz-DeChoudens S, Ortiz-Ortiz P, Pagán-Torres H, Pérez-Afanador D, Quintana-Torres EM, Ramírez-Aponte EG, Riascos-Cuero C, Rivera-Llovet MS, Rivera-Pagán IT, Rivera-Vicéns RE, Robles-Juarbe F, Rodríguez-Bonilla L, Rodríguez-Echevarría BO, Rodríguez-García PM, Rodríguez-Laboy AE, Rodríguez-Santiago S, Rojas-Vargas ML, Rubio-Marrero EN, Santiago-Colón A, Santiago-Ortiz JL, Santos-Ramos CE, Serrano-González J, Tamayo-Figueroa AM, Tascón-Peñaranda EP, Torres-Castillo JL, Valentín-Feliciano NA, Valentín-Feliciano YM, Vargas-Barreto NM, Vélez-Vázquez M, Vilanova-Vélez LR, Zambrana-Echevarría C, MacKinnon C, Chung HM, Kay C, Pinto A, Kopp OR, Burkhardt J, Harward C, Allen R, Bhat P, Chang JH, Chen Y, Chesley C, Cohn D, DuPuis D, Fasano M, Fazzio N, Gavinski K, Gebreyesus H, Giarla T, Gostelow M, Greenstein R, Gunasinghe H, Hanson C, Hay A, He TJ, Homa K, Howe R, Howenstein J, Huang H, Khatri A, Kim YL, Knowles O, Kong S, Krock R, Kroll M, Kuhn J, Kwong M, Lee B, Lee R, Levine K, Li Y, Liu B, Liu L, Liu M, Lousararian A, Ma J, Mallya A, Manchee C, Marcus J, McDaniel S, Miller ML, Molleston JM, Diez CM, Ng P, Ngai N, Nguyen H, Nylander A, Pollack J, Rastogi S, Reddy H, Regenold N, Sarezky J, Schultz M, Shim J, Skorupa T, Smith K, Spencer SJ, Srikanth P, Stancu G, Stein AP, Strother M, Sudmeier L, Sun M, Sundaram V, Tazudeen N, Tseng A, Tzeng A, Venkat R, Venkataram S, Waldman L, Wang T, Yang H, Yu JY, Zheng Y, Preuss ML, Garcia A, Juergens M, Morris RW, Nagengast AA, Azarewicz J, Carr TJ, Chichearo N, Colgan M, Donegan M, Gardner B, Kolba N, Krumm JL, Lytle S, MacMillian L, Miller M, Montgomery A, Moretti A, Offenbacker B, Polen M, Toth J, Woytanowski J, Kadlec L, Crawford J, Spratt ML, Adams AL, Barnard BK, Cheramie MN, Eime AM, Golden KL, Hawkins AP, Hill JE, Kampmeier JA, Kern CD, Magnuson EE, Miller AR, Morrow CM, Peairs JC, Pickett GL, Popelka SA, Scott AJ, Teepe EJ, TerMeer KA, Watchinski CA, Watson LA, Weber RE, Woodard KA, Barnard DC, Appiah I, Giddens MM, McNeil GP, Adebayo A, Bagaeva K, Chinwong J, Dol C, George E, Haltaufderhyde K, Haye J, Kaur M, Semon M, Serjanov D, Toorie A, Wilson C, Riddle NC, Buhler J, Mardis ER, and Elgin SC

Subjects
Animals, Codon, Computational Biology, DNA Transposable Elements, Drosophila melanogaster genetics, Exons, Gene Rearrangement, Heterochromatin, Introns, Molecular Sequence Annotation, Polytene Chromosomes, Repetitive Sequences, Nucleic Acid, Selection, Genetic, Species Specificity, Drosophila genetics, Drosophila Proteins genetics, Evolution, Molecular, Genome, Genomics
Abstract

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Published
2015
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34. Nucleocytoplasmic shuttling of galectin-3.

Author

Arnoys EJ, Ackerman CM, and Wang JL

Subjects
Active Transport, Cell Nucleus, Animals, Cell Fusion, Galectin 3 genetics, Humans, Mice, Microscopy, Fluorescence, NIH 3T3 Cells, Polyethylene Glycols pharmacology, Transfection, Cell Nucleus metabolism, Cytoplasm metabolism, Galectin 3 metabolism
Abstract

A large number of observations on the nuclear versus cytoplasmic distribution of galectin-3 have been reported, correlating the presence or absence of the protein in a particular compartment of the cell to various parameters such as source of the cells under study, specific cell type, culture conditions, proliferation status of the cell/culture, or neoplastic transformation. In fact, galectin-3 exhibits the phenomenon of nucleocytoplasmic shuttling, defined as the repeated bidirectional movement of a protein across the nuclear pore complex. Nevertheless, the finding that galectin-3 can show a predominantly nuclear localization under one set of conditions and a prominent cytoplasmic localization under other conditions suggests specific and regulated mechanisms of balance between cytoplasmic anchorage, nuclear import, nuclear retention, and nuclear export. One key consideration in the understanding of these processes is the definition of the signals and receptors that mediate the transport. In this chapter, we describe the experimental procedures that have allowed us to document the phenomenon of nucleocytoplasmic shuttling and the identification of the nuclear localization signal as well as the nuclear export signal.

Published
2015
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