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2. Next-generation large-scale binary protein interaction network for Drosophila melanogaster

Author

Tang, Hong-Wen, Spirohn, Kerstin, Hu, Yanhui, Hao, Tong, Kovács, István A., Gao, Yue, Binari, Richard, Yang-Zhou, Donghui, Wan, Kenneth H., Bader, Joel S., Balcha, Dawit, Bian, Wenting, Booth, Benjamin W., Coté, Atina G., de Rouck, Steffi, Desbuleux, Alice, Goh, Kah Yong, Kim, Dae-Kyum, Knapp, Jennifer J., Lee, Wen Xing, Lemmens, Irma, Li, Cathleen, Li, Mian, Li, Roujia, Lim, Hyobin Julianne, Liu, Yifang, Luck, Katja, Markey, Dylan, Pollis, Carl, Rangarajan, Sudharshan, Rodiger, Jonathan, Schlabach, Sadie, Shen, Yun, Sheykhkarimli, Dayag, TeeKing, Bridget, Roth, Frederick P., Tavernier, Jan, Calderwood, Michael A., Hill, David E., Celniker, Susan E., Vidal, Marc, Perrimon, Norbert, and Mohr, Stephanie E.

Published
2023
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4. Manipulating the 3D organization of the largest synthetic yeast chromosome

Author

Accardo, Ryan, Brammer Basta, Leighanne A., Bello, Nicholas R., Cai, Lousanna, Cerritos, Stephanie, Cornwell, MacIntosh, D’Amato, Anthony, Hacker, Maria, Hersey, Kenneth, Kennedy, Emma, Kianercy, Ardeshir, Kim, Dohee, McCutcheon, Griffin, McGirr, Kimiko, Meaney, Nora, Nimer, Maisa, Sabbatini, Carla, Scheifele, Lisa Z., Shores, Lucas S., Silvestrone, Cassandra, Snee, Arden, Spina, Antonio, Staiti, Anthony, Stuver, Matt, Tian, Elli, Whearty, Danielle, Zhao, Calvin, Zeller, Karen, Zhang, Weimin, Lazar-Stefanita, Luciana, Yamashita, Hitoyoshi, Shen, Michael J., Mitchell, Leslie A., Kurasawa, Hikaru, Lobzaev, Evgenii, Fanfani, Viola, Haase, Max A.B., Sun, Xiaoji, Jiang, Qingwen, Goldberg, Gregory W., Ichikawa, David M., Lauer, Stephanie L., McCulloch, Laura H., Easo, Nicole, Lin, S. Jiaming, Camellato, Brendan R., Zhu, Yinan, Cai, Jitong, Xu, Zhuwei, Zhao, Yu, Sacasa, Maya, Noyes, Marcus B., Bader, Joel S., Deutsch, Samuel, Stracquadanio, Giovanni, Aizawa, Yasunori, Dai, Junbiao, and Boeke, Jef D.

Published
2023
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5. An expanded universe of cancer targets.

Author

Hahn, William C, Bader, Joel S, Braun, Theodore P, Califano, Andrea, Clemons, Paul A, Druker, Brian J, Ewald, Andrew J, Fu, Haian, Jagu, Subhashini, Kemp, Christopher J, Kim, William, Kuo, Calvin J, McManus, Michael, B Mills, Gordon, Mo, Xiulei, Sahni, Nidhi, Schreiber, Stuart L, Talamas, Jessica A, Tamayo, Pablo, Tyner, Jeffrey W, Wagner, Bridget K, Weiss, William A, Gerhard, Daniela S, and Cancer Target Discovery and Development Network

Subjects
Cancer Target Discovery and Development Network, Animals, Humans, Neoplasms, Disease Models, Animal, Drug Delivery Systems, Genomics, Tumor Escape, Clinical Trials as Topic, Tumor Microenvironment, Biotechnology, Rare Diseases, Cancer, Orphan Drug, Genetics, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.

Published
2021

6. Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions

Author

Zhao, Yu, Coelho, Camila, Hughes, Amanda L., Lazar-Stefanita, Luciana, Yang, Sandy, Brooks, Aaron N., Walker, Roy S.K., Zhang, Weimin, Lauer, Stephanie, Hernandez, Cindy, Cai, Jitong, Mitchell, Leslie A., Agmon, Neta, Shen, Yue, Sall, Joseph, Fanfani, Viola, Jalan, Anavi, Rivera, Jordan, Liang, Feng-Xia, Bader, Joel S., Stracquadanio, Giovanni, Steinmetz, Lars M., Cai, Yizhi, and Boeke, Jef D.

Published
2023
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7. Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

Author

Adoff, Greg, Ahn, Ju Young, Annadanam, Anvesh, Annadanam, Surekha, Berger, Henri, Chen, Yi, Chickering, Michael, D’Avino, Andrew, Fishman, Oren, Im, Jay, Kim, Sangmin, Kim, Sunghan, Lim, Hong Seo, Meyer, Lauren, Moyer, Allison, Murphy, Natalie A., Natov, Peter, Radley, Arthur, Scheifele, Lisa, Tripathy, Arushi, Vergara Greeno, Rebeca, Wang, Tony, Wilkerson, Nick, Zeller, Karen, Zheng, Tony, Zhou, Vivian, Luo, Jingchuan, Vale-Silva, Luis A., Raghavan, Adhithi R., Mercy, Guillaume, Heldrich, Jonna, Sun, Xiaoji, Li, Mingyu Kenneth, Zhang, Weimin, Agmon, Neta, Yang, Kun, Cai, Jitong, Stracquadanio, Giovanni, Thierry, Agnès, Zhao, Yu, Coelho, Camila, McCulloch, Laura H., Lauer, Stephanie, Kaback, David B., Bader, Joel S., Mitchell, Leslie A., Mozziconacci, Julien, Koszul, Romain, Hochwagen, Andreas, and Boeke, Jef D.

Published
2023
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8. Context-dependent neocentromere activity in synthetic yeast chromosome VIII

Author

Anne, Lajari, Barger, James S., Belkaya, Naz, Boulier, Kristin, Butler, Kirk, Callaghan, Melanie, Chang, Calvin, Chen, Janice, Chen, Xueni Jennifer, Cho, In Young, Choi, Elliot, Choi, Woo Jin, Chuang, James, Cook, Ashley L., Cooper, Eric, Culbertson, Nicholas Timothy, Dunn, Jessilyn, Floria, Charlotte, Grogan Anderson, Breeana, Held, Nathalie P., Hsiao, Emily, Igwe, Joseph-Kevin, Kang, Koeun, Karanxha, Joana, Kelly, Marie, Khakhar, Arjun, Khunsriraksakul, Chachrit, Kim, John J., Kim, Dong, Kim, Jin Wan, Lamb, Alex, Lee, David Sung Han, Lee, Yoon Kyung, Lim, Jongseuk, Liu, Steffi, Lopez, Jeremy, Lu, Zhen A., Ma, Henry, Mandel, Jordan A., Mao, Jessica, Matelsky, Jordan, Merran, Jonathan, Mohan, Rishikesh, Montoya, Christopher, Murugan, Sindurathy, Ni, Lisa, Oh, Won Chan, Park, Youngrok, Paulsen, Laura, Phillips, Nick, Pinglay, Sudarshan, Rajan, Vikram Aditya, Ransom, Garrett, Rhoads, Erin, Sanna, Praneeth, Scher, Emily, Shah, Jinesh, Sharma, Ashwyn, Shepardson, Maya C., Song, Joanne, Sontha, Sainikhil, Srinivas, Venkatesh, Tan, Scott, Tu, Ang A., Uhl, Skyler, Xiaoyue, Wang, Yu, Fangzhou, Yu, Justine, Zhu, Amadeus, Lauer, Stephanie, Luo, Jingchuan, Lazar-Stefanita, Luciana, Zhang, Weimin, McCulloch, Laura H., Fanfani, Viola, Lobzaev, Evgenii, Haase, Max A.B., Easo, Nicole, Zhao, Yu, Cai, Jitong, Bader, Joel S., Stracquadanio, Giovanni, and Boeke, Jef D.

Published
2023
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10. Consequences of a telomerase-related fitness defect and chromosome substitution technology in yeast synIX strains

Author

Anderson, Breeana G., Apaw, Abena, Bohutskyi, Pavlo, Buchanan, Erin, Chang, Daniel, Chen, Melinda, Cooper, Eric, Deliere, Amanda, Drakos, Kallie, Dubin, Justin, Fernandez, Christopher, Guo, Zheyuan, Harrelson, Thomas, Lee, Dongwon, McDade, Jessica, Melamed, Scott, Müller, Héloise, Murali, Adithya, Niño Rivera, José U., Patel, Mira, Rodley, Mary, Schwarz, Jenna, Shelat, Nirav, Sims, Josh S., Steinberg, Barrett, Steinhardt, James, Trivedi, Rishi K., Von Dollen, Christopher, Wang, Tianyi, Wong, Remus, Xu, Yijie, Young, Noah, Zeller, Karen, Zhang, Allen, McCulloch, Laura H., Sambasivam, Vijayan, Hughes, Amanda L., Annaluru, Narayana, Ramalingam, Sivaprakash, Fanfani, Viola, Lobzaev, Evgenii, Mitchell, Leslie A., Cai, Jitong, Jiang, Hua, LaCava, John, Taylor, Martin S., Bishai, William R., Stracquadanio, Giovanni, Steinmetz, Lars M., Bader, Joel S., Zhang, Weimin, Boeke, Jef D., and Chandrasegaran, Srinivasan

Published
2023
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11. Synthetic yeast chromosome XI design provides a testbed for the study of extrachromosomal circular DNA dynamics

Author

Blount, Benjamin A., Lu, Xinyu, Driessen, Maureen R.M., Jovicevic, Dejana, Sanchez, Mateo I., Ciurkot, Klaudia, Zhao, Yu, Lauer, Stephanie, McKiernan, Robert M., Gowers, Glen-Oliver F., Sweeney, Fiachra, Fanfani, Viola, Lobzaev, Evgenii, Palacios-Flores, Kim, Walker, Roy S.K., Hesketh, Andy, Cai, Jitong, Oliver, Stephen G., Cai, Yizhi, Stracquadanio, Giovanni, Mitchell, Leslie A., Bader, Joel S., Boeke, Jef D., and Ellis, Tom

Published
2023
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12. Parallel laboratory evolution and rational debugging reveal genomic plasticity to S. cerevisiae synthetic chromosome XIV defects

Author

Williams, Thomas C., Kroukamp, Heinrich, Xu, Xin, Wightman, Elizabeth L.I., Llorente, Briardo, Borneman, Anthony R., Carpenter, Alexander C., Van Wyk, Niel, Meier, Felix, Collier, Thomas R.V., Espinosa, Monica I., Daniel, Elizabeth L., Walker, Roy S.K., Cai, Yizhi, Nevalainen, Helena K.M., Curach, Natalie C., Deveson, Ira W., Mercer, Timothy R., Johnson, Daniel L., Mitchell, Leslie A., Bader, Joel S., Stracquadanio, Giovanni, Boeke, Jef D., Goold, Hugh D., Pretorius, Isak S., and Paulsen, Ian T.

Published
2023
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13. Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

Author

Shen, Yue, Gao, Feng, Wang, Yun, Wang, Yuerong, Zheng, Ju, Gong, Jianhui, Zhang, Jintao, Luo, Zhouqing, Schindler, Daniel, Deng, Yang, Ding, Weichao, Lin, Tao, Swidah, Reem, Zhao, Hongcui, Jiang, Shuangying, Zeng, Cheng, Chen, Shihong, Chen, Tai, Wang, Yong, Luo, Yisha, Mitchell, Leslie, Bader, Joel S., Zhang, Guojie, Shen, Xia, Wang, Jian, Fu, Xian, Dai, Junbiao, Boeke, Jef D., Yang, Huanming, Xu, Xun, and Cai, Yizhi

Published
2023
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14. Genetic interaction mapping informs integrative structure determination of protein complexes

Author

Braberg, Hannes, Echeverria, Ignacia, Bohn, Stefan, Cimermancic, Peter, Shiver, Anthony, Alexander, Richard, Xu, Jiewei, Shales, Michael, Dronamraju, Raghuvar, Jiang, Shuangying, Dwivedi, Gajendradhar, Bogdanoff, Derek, Chaung, Kaitlin K, Hüttenhain, Ruth, Wang, Shuyi, Mavor, David, Pellarin, Riccardo, Schneidman, Dina, Bader, Joel S, Fraser, James S, Morris, John, Haber, James E, Strahl, Brian D, Gross, Carol A, Dai, Junbiao, Boeke, Jef D, Sali, Andrej, and Krogan, Nevan J

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Histones, Multiprotein Complexes, Mutation, Protein Conformation, Protein Interaction Mapping, Protein Interaction Maps, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, General Science & Technology
Abstract

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations.

Published
2020

15. Longitudinal change in mitochondrial heteroplasmy exhibits positive selection for deleterious variants

Author

Kuiper, Lieke M., primary, Shi, Wen, additional, Verlouw, Joost, additional, Hong, Yun Soo, additional, Arp, Pascal, additional, Puiu, Daniela, additional, Broer, Linda, additional, Xie, Jiaqi, additional, Newcomb, Charles, additional, Rich, Stephen S., additional, Taylor, Kent D., additional, Rotter, Jerome I., additional, Bader, Joel S., additional, Guallar, Eliseo, additional, van Meurs, Joyce B.J., additional, and Arking, Dan E., additional

Published
2024
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16. Fast and reliable inference algorithm for hierarchical stochastic block models

Author

Park, Yongjin and Bader, Joel S.

Subjects
Statistics - Machine Learning
Abstract

Network clustering reveals the organization of a network or corresponding complex system with elements represented as vertices and interactions as edges in a (directed, weighted) graph. Although the notion of clustering can be somewhat loose, network clusters or groups are generally considered as nodes with enriched interactions and edges sharing common patterns. Statistical inference often treats groups as latent variables, with observed networks generated from latent group structure, termed a stochastic block model. Regardless of the definitions, statistical inference can be either translated to modularity maximization, which is provably an NP-complete problem. Here we present scalable and reliable algorithms that recover hierarchical stochastic block models fast and accurately. Our algorithm scales almost linearly in number of edges, and inferred models were more accurate that other scalable methods.

Published
2017

17. Prioritizing drug targets by perturbing biological network response functions.

Author

Perrone, Matthew C., Lerner, Michael G., Dunworth, Matthew, Ewald, Andrew J., and Bader, Joel S.

Subjects
DRUG target, METASTATIC breast cancer, BIOLOGICAL networks, SMALL molecules, PROTEIN-protein interactions, PERTURBATION theory
Abstract

Therapeutic interventions are designed to perturb the function of a biological system. However, there are many types of proteins that cannot be targeted with conventional small molecule drugs. Accordingly, many identified gene-regulatory drivers and downstream effectors are currently undruggable. Drivers and effectors are often connected by druggable signaling and regulatory intermediates. Methods to identify druggable intermediates therefore have general value in expanding the set of targets available for hypothesis-driven validation. Here we identify and prioritize potential druggable intermediates by developing a network perturbation theory, termed NetPert, for response functions of biological networks. Dynamics are defined by a network structure in which vertices represent genes and proteins, and edges represent gene-regulatory interactions and protein-protein interactions. Perturbation theory for network dynamics prioritizes targets that interfere with signaling from driver to response genes. Applications to organoid models for metastatic breast cancer demonstrate the ability of this mathematical framework to identify and prioritize druggable intermediates. While the short-time limit of the perturbation theory resembles betweenness centrality, NetPert is superior in generating target rankings that correlate with previous wet-lab assays and are more robust to incomplete or noisy network data. NetPert also performs better than a related graph diffusion approach. Wet-lab assays demonstrate that drugs for targets identified by NetPert, including targets that are not themselves differentially expressed, are active in suppressing additional metastatic phenotypes. Author summary: Many therapies, especially small molecule drugs, inhibit the activity of a protein target. Not all proteins are druggable, however. When the proteins known to be involved in a disease process are not druggable, identifying a good target is difficult. In cancer, for example, the somatic driver mutations are often known, and the downstream changes in gene expression may be measured, but the driver gene and response genes may not be druggable. Here we present a method, NetPert, that selects candidate drug targets based on their ability to perturb interactions connecting a driver gene to response genes. Drugs already known to target these candidates are also reported. Applications to mouse models for metastatic breast cancer show that targets ranked highly by this method are highly active in wet-lab assays for dissemination and metastatic outgrowth. The NetPert method provides an interpretable data-driven approach to target selection and drug prioritization. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Morphology-guided transcriptomic analysis of human pancreatic cancer organoids reveals microenvironmental signals that enhance invasion

Author

Jeong, Yea Ji, Knutsdottir, Hildur, Shojaeian, Fatemeh, Lerner, Michael G., Wissler, Maria F., Henriet, Elodie, Ng, Tammy, Datta, Shalini, Navarro-Serer, Bernat, Chianchiano, Peter, Kinny-Koster, Benedict, Zimmerman, Jacquelyn W., Stein-O'Brien, Genevieve, Gaida, Matthias M., Eshleman, James R., Lin, Ming-Tseh, Fertig, Elana J., Ewald, Andrew J., Bader, Joel S., and Wood, Laura D.

Subjects
Oncology, Experimental, Gene expression -- Research, Organs, Culture of -- Usage, Metastasis -- Genetic aspects -- Development and progression -- Models, Cancer -- Research, Pancreatic cancer -- Genetic aspects -- Development and progression -- Models, Health care industry
Abstract

Pancreatic ductal adenocarcinoma (PDAC) frequently presents with metastasis, but the molecular programs in human PDAC cells that drive invasion are not well understood. Using an experimental pipeline enabling PDAC organoid isolation and collection based on invasive phenotype, we assessed the transcriptomic programs associated with invasion in our organoid model. We identified differentially expressed genes in invasive organoids compared with matched noninvasive organoids from the same patients, and we confirmed that the encoded proteins were enhanced in organoid invasive protrusions. We identified 3 distinct transcriptomic groups in invasive organoids, 2 of which correlated directly with the morphological invasion patterns and were characterized by distinct upregulated pathways. Leveraging publicly available single-cell RNA-sequencing data, we mapped our transcriptomic groups onto human PDAC tissue samples, highlighting differences in the tumor microenvironment between transcriptomic groups and suggesting that non-neoplastic cells in the tumor microenvironment can modulate tumor cell invasion. To further address this possibility, we performed computational ligand-receptor analysis and validated the impact of multiple ligands (TGF-[beta]1, IL-6, CXCL12, MMP9) on invasion and gene expression in an independent cohort of fresh human PDAC organoids. Our results identify molecular programs driving morphologically defined invasion patterns and highlight the tumor microenvironment as a potential modulator of these programs., Introduction Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis that is due, at least in part, to its late stage at diagnosis, with almost 90% of patients presenting with metastasis [...]

Published
2023
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19. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author

van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, and Ferrucci, Luigi

Subjects
Biological Sciences, Genetics, Human Genome, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Atrial Function, Atrioventricular Node, Electrocardiography, Electrophysiological Phenomena, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Risk Factors
Abstract

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

Published
2018

20. Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure

Author

Peterson, Tess Eirene, primary, Hahn, Virginia Shalkey, additional, Moaddel, Ruin, additional, Zhu, Min, additional, Haberlen, Sabina A., additional, Palella, Frank J., additional, Plankey, Michael, additional, Bader, Joel S, additional, Lima, Joao A.C., additional, Gerszten, Robert E, additional, Rotter, Jerome I. I., additional, Rich, Stephen S. S., additional, Heckbert, Susan R., additional, Kirk, Gregory D., additional, Piggott, Damani A, additional, Ferrucci, Luigi, additional, Margolick, Joseph, additional, Brown, Todd T., additional, Wu, Katherine C., additional, and Post, Wendy S., additional

Published
2024
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21. Ensemble Detection of DNA Engineering Signatures.

Author

Adler, Aaron, Bader, Joel S., Basnight, Brian, Booth, Benjamin W., Cai, Jitong, Cho, Elizabeth, Collins, Joseph H., Ge, Yuchen, Grothendieck, John, Keating, Kevin, Marshall, Tyler, Persikov, Anton, Scott, Helen, Siegelmann, Roy, Singh, Mona, Taggart, Allison, Toll, Benjamin, Wan, Kenneth H., Wyschogrod, Daniel, and Yaman, Fusun

Published
2024
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22. Context-dependent neocentromere activity in synthetic yeast chromosome VIII

Author

Lauer, Stephanie, primary, Luo, Jingchuan, additional, Lazar-Stefanita, Luciana, additional, Zhang, Weimin, additional, McCulloch, Laura H., additional, Fanfani, Viola, additional, Lobzaev, Evgenii, additional, Haase, Max A.B., additional, Easo, Nicole, additional, Zhao, Yu, additional, Yu, Fangzhou, additional, Cai, Jitong, additional, Bader, Joel S., additional, Stracquadanio, Giovanni, additional, Boeke, Jef D., additional, Anne, Lajari, additional, Barger, James S., additional, Belkaya, Naz, additional, Boulier, Kristin, additional, Butler, Kirk, additional, Callaghan, Melanie, additional, Chang, Calvin, additional, Chen, Janice, additional, Chen, Xueni Jennifer, additional, Cho, In Young, additional, Choi, Elliot, additional, Choi, Woo Jin, additional, Chuang, James, additional, Cook, Ashley L., additional, Cooper, Eric, additional, Culbertson, Nicholas Timothy, additional, Dunn, Jessilyn, additional, Floria, Charlotte, additional, Grogan Anderson, Breeana, additional, Held, Nathalie P., additional, Hsiao, Emily, additional, Igwe, Joseph-Kevin, additional, Kang, Koeun, additional, Karanxha, Joana, additional, Kelly, Marie, additional, Khakhar, Arjun, additional, Khunsriraksakul, Chachrit, additional, Kim, John J., additional, Kim, Dong, additional, Kim, Jin Wan, additional, Lamb, Alex, additional, Lee, David Sung Han, additional, Lee, Yoon Kyung, additional, Lim, Jongseuk, additional, Liu, Steffi, additional, Lopez, Jeremy, additional, Lu, Zhen A., additional, Ma, Henry, additional, Mandel, Jordan A., additional, Mao, Jessica, additional, Matelsky, Jordan, additional, Merran, Jonathan, additional, Mohan, Rishikesh, additional, Montoya, Christopher, additional, Murugan, Sindurathy, additional, Ni, Lisa, additional, Oh, Won Chan, additional, Park, Youngrok, additional, Paulsen, Laura, additional, Phillips, Nick, additional, Pinglay, Sudarshan, additional, Rajan, Vikram Aditya, additional, Ransom, Garrett, additional, Rhoads, Erin, additional, Sanna, Praneeth, additional, Scher, Emily, additional, Shah, Jinesh, additional, Sharma, Ashwyn, additional, Shepardson, Maya C., additional, Song, Joanne, additional, Sontha, Sainikhil, additional, Srinivas, Venkatesh, additional, Tan, Scott, additional, Tu, Ang A., additional, Uhl, Skyler, additional, Xiaoyue, Wang, additional, Yu, Justine, additional, and Zhu, Amadeus, additional

Published
2023
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23. Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

Author

Luo, Jingchuan, primary, Vale-Silva, Luis A., additional, Raghavan, Adhithi R., additional, Mercy, Guillaume, additional, Heldrich, Jonna, additional, Sun, Xiaoji, additional, Li, Mingyu Kenneth, additional, Zhang, Weimin, additional, Agmon, Neta, additional, Yang, Kun, additional, Cai, Jitong, additional, Stracquadanio, Giovanni, additional, Thierry, Agnès, additional, Zhao, Yu, additional, Coelho, Camila, additional, McCulloch, Laura H., additional, Lauer, Stephanie, additional, Kaback, David B., additional, Bader, Joel S., additional, Mitchell, Leslie A., additional, Mozziconacci, Julien, additional, Koszul, Romain, additional, Hochwagen, Andreas, additional, Boeke, Jef D., additional, Adoff, Greg, additional, Ahn, Ju Young, additional, Annadanam, Anvesh, additional, Annadanam, Surekha, additional, Berger, Henri, additional, Chen, Yi, additional, Chickering, Michael, additional, D’Avino, Andrew, additional, Fishman, Oren, additional, Im, Jay, additional, Kim, Sangmin, additional, Kim, Sunghan, additional, Lim, Hong Seo, additional, Meyer, Lauren, additional, Moyer, Allison, additional, Murphy, Natalie A., additional, Natov, Peter, additional, Radley, Arthur, additional, Scheifele, Lisa, additional, Tripathy, Arushi, additional, Vergara Greeno, Rebeca, additional, Wang, Tony, additional, Wilkerson, Nick, additional, Zeller, Karen, additional, Zheng, Tony, additional, and Zhou, Vivian, additional

Published
2023
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24. Consequences of a telomerase-related fitness defect and chromosome substitution technology in yeast synIX strains

Author

McCulloch, Laura H., primary, Sambasivam, Vijayan, additional, Hughes, Amanda L., additional, Annaluru, Narayana, additional, Ramalingam, Sivaprakash, additional, Fanfani, Viola, additional, Lobzaev, Evgenii, additional, Mitchell, Leslie A., additional, Cai, Jitong, additional, Jiang, Hua, additional, LaCava, John, additional, Taylor, Martin S., additional, Bishai, William R., additional, Stracquadanio, Giovanni, additional, Steinmetz, Lars M., additional, Bader, Joel S., additional, Zhang, Weimin, additional, Boeke, Jef D., additional, Chandrasegaran, Srinivasan, additional, Anderson, Breeana G., additional, Apaw, Abena, additional, Bohutskyi, Pavlo, additional, Buchanan, Erin, additional, Chang, Daniel, additional, Chen, Melinda, additional, Cooper, Eric, additional, Deliere, Amanda, additional, Drakos, Kallie, additional, Dubin, Justin, additional, Fernandez, Christopher, additional, Guo, Zheyuan, additional, Harrelson, Thomas, additional, Lee, Dongwon, additional, McDade, Jessica, additional, Melamed, Scott, additional, Müller, Héloise, additional, Murali, Adithya, additional, Niño Rivera, José U., additional, Patel, Mira, additional, Rodley, Mary, additional, Schwarz, Jenna, additional, Shelat, Nirav, additional, Sims, Josh S., additional, Steinberg, Barrett, additional, Steinhardt, James, additional, Trivedi, Rishi K., additional, Von Dollen, Christopher, additional, Wang, Tianyi, additional, Wong, Remus, additional, Xu, Yijie, additional, Young, Noah, additional, Zeller, Karen, additional, and Zhang, Allen, additional

Published
2023
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25. Manipulating the 3D organization of the largest synthetic yeast chromosome

Author

Zhang, Weimin, primary, Lazar-Stefanita, Luciana, additional, Yamashita, Hitoyoshi, additional, Shen, Michael J., additional, Mitchell, Leslie A., additional, Kurasawa, Hikaru, additional, Lobzaev, Evgenii, additional, Fanfani, Viola, additional, Haase, Max A.B., additional, Sun, Xiaoji, additional, Jiang, Qingwen, additional, Goldberg, Gregory W., additional, Ichikawa, David M., additional, Lauer, Stephanie L., additional, McCulloch, Laura H., additional, Easo, Nicole, additional, Lin, S. Jiaming, additional, Camellato, Brendan R., additional, Zhu, Yinan, additional, Cai, Jitong, additional, Xu, Zhuwei, additional, Zhao, Yu, additional, Sacasa, Maya, additional, Noyes, Marcus B., additional, Bader, Joel S., additional, Deutsch, Samuel, additional, Stracquadanio, Giovanni, additional, Aizawa, Yasunori, additional, Dai, Junbiao, additional, Boeke, Jef D., additional, Accardo, Ryan, additional, Brammer Basta, Leighanne A, additional, Bello, Nicholas R., additional, Cai, Lousanna, additional, Cerritos, Stephanie, additional, Cornwell, MacIntosh, additional, D’Amato, Anthony, additional, Hacker, Maria, additional, Hersey, Kenneth, additional, Kennedy, Emma, additional, Kianercy, Ardeshir, additional, Kim, Dohee, additional, McCutcheon, Griffin, additional, McGirr, Kimiko, additional, Meaney, Nora, additional, Nimer, Maisa, additional, Sabbatini, Carla, additional, Scheifele, Lisa, additional, Shores, Lucas S., additional, Silvestrone, Cassandra, additional, Snee, Arden, additional, Spina, Antonio, additional, Staiti, Anthony, additional, Stuver, Matt, additional, Tian, Elli, additional, Whearty, Danielle, additional, Zhao, Calvin, additional, and Zeller, Karen, additional

Published
2023
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27. E-cadherin is required for metastasis in multiple models of breast cancer

Author

Padmanaban, Veena, Krol, Ilona, Suhail, Yasir, Szczerba, Barbara M., Aceto, Nicola, Bader, Joel S., and Ewald, Andrew J.

Subjects
Cadherins -- Analysis, Metastasis -- Analysis -- Patient outcomes, Breast cancer -- Models -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Metastasis is the major driver of death in patients with cancer. Invasion of surrounding tissues and metastasis have been proposed to initiate following loss of the intercellular adhesion protein, E-cadherin.sup.1,2, on the basis of inverse correlations between in vitro migration and E-cadherin levels.sup.3. However, this hypothesis is inconsistent with the observation that most breast cancers are invasive ductal carcinomas and express E-cadherin in primary tumours and metastases.sup.4. To resolve this discrepancy, we tested the genetic requirement for E-cadherin in metastasis using mouse and human models of both luminal and basal invasive ductal carcinomas. Here we show that E-cadherin promotes metastasis in diverse models of invasive ductal carcinomas. While loss of E-cadherin increased invasion, it also reduced cancer cell proliferation and survival, circulating tumour cell number, seeding of cancer cells in distant organs and metastasis outgrowth. Transcriptionally, loss of E-cadherin was associated with upregulation of genes involved in transforming growth factor-[beta] (TGF[beta]), reactive oxygen species and apoptosis signalling pathways. At the cellular level, disseminating E-cadherin-negative cells exhibited nuclear enrichment of SMAD2/3, oxidative stress and increased apoptosis. Colony formation of E-cadherin-negative cells was rescued by inhibition of TGF[beta]-receptor signalling, reactive oxygen accumulation or apoptosis. Our results reveal that E-cadherin acts as a survival factor in invasive ductal carcinomas during the detachment, systemic dissemination and seeding phases of metastasis by limiting reactive oxygen-mediated apoptosis. Identifying molecular strategies to inhibit E-cadherin-mediated survival in metastatic breast cancer cells may have potential as a therapeutic approach for breast cancer. Although E-cadherin loss promotes tumour-cell invasion in mouse and human models of invasive ductal carcinoma, E-cadherin expression prevents oxidative-stress-mediated apoptosis during detachment and is essential for metastasis., Author(s): Veena Padmanaban [sup.1] , Ilona Krol [sup.2] , Yasir Suhail [sup.3] , Barbara M. Szczerba [sup.2] , Nicola Aceto [sup.2] , Joel S. Bader [sup.3] , Andrew J. Ewald [...]

Published
2019
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30. RNA-Seq optimization with eQTL gold standards.

Author

Ellis, Shannon E, Gupta, Simone, Ashar, Foram N, Bader, Joel S, West, Andrew B, and Arking, Dan E

Subjects
Brain, Blood, Humans, Reproducibility of Results, Chromosome Mapping, Sequence Analysis, RNA, Quantitative Trait Loci, Reference Standards, Genotyping Techniques, Biological Sciences, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics
Abstract

BackgroundRNA-Sequencing (RNA-Seq) experiments have been optimized for library preparation, mapping, and gene expression estimation. These methods, however, have revealed weaknesses in the next stages of analysis of differential expression, with results sensitive to systematic sample stratification or, in more extreme cases, to outliers. Further, a method to assess normalization and adjustment measures imposed on the data is lacking.ResultsTo address these issues, we utilize previously published eQTLs as a novel gold standard at the center of a framework that integrates DNA genotypes and RNA-Seq data to optimize analysis and aid in the understanding of genetic variation and gene expression. After detecting sample contamination and sequencing outliers in RNA-Seq data, a set of previously published brain eQTLs was used to determine if sample outlier removal was appropriate. Improved replication of known eQTLs supported removal of these samples in downstream analyses. eQTL replication was further employed to assess normalization methods, covariate inclusion, and gene annotation. This method was validated in an independent RNA-Seq blood data set from the GTEx project and a tissue-appropriate set of eQTLs. eQTL replication in both data sets highlights the necessity of accounting for unknown covariates in RNA-Seq data analysis.ConclusionAs each RNA-Seq experiment is unique with its own experiment-specific limitations, we offer an easily-implementable method that uses the replication of known eQTLs to guide each step in one's data analysis pipeline. In the two data sets presented herein, we highlight not only the necessity of careful outlier detection but also the need to account for unknown covariates in RNA-Seq experiments.

Published
2013

31. DNA transport by a micromachined Brownian ratchet device

Author

Bader, Joel S., Hammond, Richard W., Henck, Steven A., Deem, Michael W., McDermott, Gregory A., Bustillo, James M., Simpson, John W., Mulhern, Gregory T., and Rothberg, Jonathan M.

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter, Quantitative Biology
Abstract

We have micromachined a silicon-chip device that transports DNA with a Brownian ratchet that rectifies the Brownian motion of microscopic particles. Transport properties for a DNA 50mer agree with theoretical predictions, and the DNA diffusion constant agrees with previous experiments. This type of micromachine could provide a generic pump or separation component for DNA or other charged species as part of a microscale lab-on-a-chip. A device with reduced feature size could produce a size-based separation of DNA molecules, with applications including the detection of single nucleotide polymorphisms., Comment: Latex: 8 pages, 4 figures

Published
1999
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32. Evolutionary implications of a power-law distribution of protein family sizes

Author

Bader, Joel S.

Subjects
Physics - Biological Physics, Quantitative Biology
Abstract

Current-day genomes bear the mark of the evolutionary processes. One of the strongest indications is the sequence homology among families of proteins that perform similar biological functions in different species. The number of proteins in a family can grow over time as genetic information is duplicated through evolution. We explore how evolution directs the size distribution of these families. Theoretical predictions for family sizes are obtained from two models, one in which individual genes duplicate and a second in which the entire genome duplicates. Predictions from these models are compared with the family size distributions for several organisms whose complete genome sequence is known. We find that protein family size distributions in nature follow a power-law distribution. Comparing these results to the model systems, we conclude that genome duplication is the dominant mechanism leading to increased genetic material in the species considered., Comment: 11 pages, 3 figures

Published
1999

33. “Perfect” designer chromosome V and behavior of a ring derivative

Author

Xie, Ze-Xiong, Li, Bing-Zhi, Mitchell, Leslie A., Wu, Yi, Qi, Xin, Jin, Zhu, Jia, Bin, Wang, Xia, Zeng, Bo-Xuan, Liu, Hui-Min, Wu, Xiao-Le, Feng, Qi, Zhang, Wen-Zheng, Liu, Wei, Ding, Ming-Zhu, Li, Xia, Zhao, Guang-Rong, Qiao, Jian-Jun, Cheng, Jing-Sheng, Zhao, Meng, Kuang, Zheng, Wang, Xuya, Martin, J. Andrew, Stracquadanio, Giovanni, Yang, Kun, Bai, Xue, Zhao, Juan, Hu, Meng-Long, Lin, Qiu-Hui, Zhang, Wen-Qian, Shen, Ming-Hua, Chen, Si, Su, Wan, Wang, En-Xu, Guo, Rui, Zhai, Fang, Guo, Xue-Jiao, Du, Hao-Xing, Zhu, Jia-Qing, Song, Tian-Qing, Dai, Jun-Jun, Li, Fei-Fei, Jiang, Guo-Zhen, Han, Shi-Lei, Liu, Shi-Yang, Yu, Zhi-Chao, Yang, Xiao-Na, Chen, Ken, Hu, Cheng, Li, Da-Shuai, Jia, Nan, Liu, Yue, Wang, Lin-Ting, Wang, Su, Wei, Xiao-Tong, Fu, Mei-Qing, Qu, Lan-Meng, Xin, Si-Yu, Liu, Ting, Tian, Kai-Ren, Li, Xue-Nan, Zhang, Jin-Hua, Song, Li-Xiang, Liu, Jin-Gui, Lv, Jia-Fei, Xu, Hang, Tao, Ran, Wang, Yan, Zhang, Ting-Ting, Deng, Ye-Xuan, Wang, Yi-Ran, Li, Ting, Ye, Guang-Xin, Xu, Xiao-Ran, Xia, Zheng-Bao, Zhang, Wei, Yang, Shi-Lan, Liu, Yi-Lin, Ding, Wen-Qi, Liu, Zhen-Ning, Zhu, Jun-Qi, Liu, Ning-Zhi, Walker, Roy, Luo, Yisha, Wang, Yun, Shen, Yue, Yang, Huanming, Cai, Yizhi, Ma, Ping-Sheng, Zhang, Chun-Ting, Bader, Joel S., Boeke, Jef D., and Yuan, Ying-Jin

Published
2017

34. 3D organization of synthetic and scrambled chromosomes

Author

Mercy, Guillaume, Mozziconacci, Julien, Scolari, Vittore F., Yang, Kun, Zhao, Guanghou, Thierry, Agnès, Luo, Yisha, Mitchell, Leslie A., Shen, Michael, Shen, Yue, Walker, Roy, Zhang, Weimin, Wu, Yi, Xie, Ze-xiong, Luo, Zhouqing, Cai, Yizhi, Dai, Junbiao, Yang, Huanming, Yuan, Ying-Jin, Boeke, Jef D., Bader, Joel S., Muller, Héloïse, and Koszul, Romain

Published
2017

35. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

Author

Shen, Yue, Wang, Yun, Chen, Tai, Gao, Feng, Gong, Jianhui, Abramczyk, Dariusz, Walker, Roy, Zhao, Hongcui, Chen, Shihong, Liu, Wei, Luo, Yisha, Müller, Carolin A., Paul-Dubois-Taine, Adrien, Alver, Bonnie, Stracquadanio, Giovanni, Mitchell, Leslie A., Luo, Zhouqing, Fan, Yanqun, Zhou, Baojin, Wen, Bo, Tan, Fengji, Wang, Yujia, Zi, Jin, Xie, Zexiong, Li, Bingzhi, Yang, Kun, Richardson, Sarah M., Jiang, Hui, French, Christopher E., Nieduszynski, Conrad A., Koszul, Romain, Marston, Adele L., Yuan, Yingjin, Wang, Jian, Bader, Joel S., Dai, Junbiao, Boeke, Jef D., Xu, Xun, Cai, Yizhi, and Yang, Huanming

Published
2017

36. Engineering the ribosomal DNA in a megabase synthetic chromosome

Author

Zhang, Weimin, Zhao, Guanghou, Luo, Zhouqing, Lin, Yicong, Wang, Lihui, Guo, Yakun, Wang, Ann, Jiang, Shuangying, Jiang, Qingwen, Gong, Jianhui, Wang, Yun, Hou, Sha, Huang, Jing, Li, Tianyi, Qin, Yiran, Dong, Junkai, Qin, Qin, Zhang, Jiaying, Zou, Xinzhi, He, Xi, Zhao, Li, Xiao, Yibo, Xu, Meng, Cheng, Erchao, Huang, Ning, Zhou, Tong, Shen, Yue, Walker, Roy, Luo, Yisha, Kuang, Zheng, Mitchell, Leslie A., Yang, Kun, Richardson, Sarah M., Wu, Yi, Li, Bing-Zhi, Yuan, Ying-Jin, Yang, Huanming, Lin, Jiwei, Chen, Guo-Qiang, Wu, Qingyu, Bader, Joel S., Cai, Yizhi, Boeke, Jef D., and Dai, Junbiao

Published
2017

37. Synthesis, debugging, and effects of synthetic chromosome consolidation : synVI and beyond

Author

Mitchell, Leslie A., Wang, Ann, Stracquadanio, Giovanni, Kuang, Zheng, Wang, Xuya, Yang, Kun, Richardson, Sarah, Martin, J. Andrew, Zhao, Yu, Walker, Roy, Luo, Yisha, Dai, Hongjiu, Dong, Kang, Tang, Zuojian, Yang, Yanling, Cai, Yizhi, Heguy, Adriana, Ueberheide, Beatrix, Fenyö, David, Dai, Junbiao, Bader, Joel S., and Boeke, Jef D.

Published
2017

38. Bug mapping and fitness testing of chemically synthesized chromosome X

Author

Wu, Yi, Li, Bing-Zhi, Zhao, Meng, Mitchell, Leslie A., Xie, Ze-Xiong, Lin, Qiu-Hui, Wang, Xia, Xiao, Wen-Hai, Wang, Ying, Zhou, Xiao, Liu, Hong, Li, Xia, Ding, Ming-Zhu, Liu, Duo, Zhang, Lu, Liu, Bao-Li, Wu, Xiao-Le, Li, Fei-Fei, Dong, Xiu-Tao, Jia, Bin, Zhang, Wen-Zheng, Jiang, Guo-Zhen, Liu, Yue, Bai, Xue, Song, Tian-Qing, Chen, Yan, Zhou, Si-Jie, Zhu, Rui-Ying, Gao, Feng, Kuang, Zheng, Wang, Xuya, Shen, Michael, Yang, Kun, Stracquadanio, Giovanni, Richardson, Sarah M., Lin, Yicong, Wang, Lihui, Walker, Roy, Luo, Yisha, Ma, Ping-Sheng, Yang, Huanming, Cai, Yizhi, Dai, Junbiao, Bader, Joel S., Boeke, Jef D., and Yuan, Ying-Jin

Published
2017

39. Design of a synthetic yeast genome

Author

Richardson, Sarah M., Mitchell, Leslie A., Stracquadanio, Giovanni, Yang, Kun, Dymond, Jessica S., DiCarlo, James E., Lee, Dongwon, Huang, Cheng Lai Victor, Chandrasegaran, Srinivasan, Cai, Yizhi, Boeke, Jef D., and Bader, Joel S.

Published
2017

43. Screening and Characterization of Aging Regulators Using Synthesized Yeast Chromosome XIII

Author

Zhou, Chun, primary, Wang, Yun, additional, Huang, Yikun, additional, An, Yongpan, additional, Wang, Yilin, additional, Zhang, Jintao, additional, Mitchell, Leslie A., additional, Bader, Joel S., additional, Cai, Yizhi, additional, Dai, Junbiao, additional, Boeke, Jef D., additional, Cai, Zhiming, additional, Xie, Zhengwei, additional, Shen, Yue, additional, and Huang, Weiren, additional

Published
2023
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45. Pervasive RNA folding is crucial for narnavirus genome maintenance.

Author

Makiha Fukuda, Jitong Cai, Bader, Joel S., and Boeke, Jef D.

Subjects
RNA, RNA analysis, GENOMES, TECHNOLOGICAL innovations, SITE-specific mutagenesis
Abstract

A synthetic biology approach toward constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. For the precise design of an artificial RNA replicon either from scratch or based on a natural RNA replicon, understanding structure-function relationships of RNA sequences is critical. However, our knowledge remains limited to a few particular structural elements intensively studied so far. Here, we conducted a series of site-directed mutagenesis studies of yeast narnaviruses ScNV20S and ScNV23S, perhaps the simplest natural autonomous RNA replicons, to identify RNA elements required for maintenance and replication. RNA structure disruption corresponding to various portions of the entire narnavirus genome suggests that pervasive RNA folding, in addition to the precise secondary structure of genome termini, is essential for maintenance of the RNA replicon in vivo. Computational RNA structure analyses suggest that this scenario likely applies to other "narna-like" viruses. This finding implies selective pressure on these simplest autonomous natural RNA replicons to fold into a unique structure that acquires both thermodynamic and biological stability. We propose the importance of pervasive RNA folding for the design of RNA replicons that could serve as a platform for in vivo continuous evolution as well as an interesting model to study the origin of life. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast

Author

Shen, Yue, primary, Gao, Feng, additional, Wang, Yun, additional, Wang, Yuerong, additional, Zheng, Ju, additional, Gong, Jianhui, additional, Zhang, Jintao, additional, Luo, Zhouqing, additional, Schindler, Daniel, additional, Deng, Yang, additional, Ding, Weichao, additional, Lin, Tao, additional, Swidah, Reem, additional, Zhao, Hongcui, additional, Jiang, Shuangying, additional, Zeng, Cheng, additional, Chen, Shihong, additional, Chen, Tai, additional, Wang, Yong, additional, Luo, Yisha, additional, Mitchell, Leslie, additional, Bader, Joel S., additional, Zhang, Guojie, additional, Shen, Xia, additional, Wang, Jian, additional, Fu, Xian, additional, Dai, Junbiao, additional, Boeke, Jef D., additional, Yang, Huanming, additional, Xu, Xun, additional, and Cai, Yizhi, additional

Published
2022
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50. Next-generation large-scale binary protein interaction network for Drosophila

Author

Tang, Hong-Wen, primary, Spirohn, Kerstin, additional, Hu, Yanhui, additional, Hao, Tong, additional, Kovács, István A., additional, Gao, Yue, additional, Binari, Richard, additional, Yang-Zhou, Donghui, additional, Wan, Kenneth H., additional, Bader, Joel S., additional, Balcha, Dawit, additional, Bian, Wenting, additional, Booth, Benjamin W., additional, Cote, Atina G., additional, De Rouck, Steffi, additional, Desbuleux, Alice, additional, Kim, Dae-Kyum, additional, Knapp, Jennifer J., additional, Lee, Wen Xing, additional, Lemmens, Irma, additional, Li, Cathleen, additional, Li, Mian, additional, Li, Roujia, additional, Lim, Hyobin Julianne, additional, Luck, Katja, additional, Markey, Dylan, additional, Pollis, Carl, additional, Rangarajan, Sudharshan, additional, Rodiger, Jonathan, additional, Schlabach, Sadie, additional, Shen, Yun, additional, TeeKing, Bridget, additional, Roth, Frederick P., additional, Tavernier, Jan, additional, Calderwood, Michael A., additional, Hill, David E., additional, Celniker, Susan E., additional, Vidal, Marc, additional, Perrimon, Norbert, additional, and Mohr, Stephanie E., additional

Published
2022
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