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167 results on '"Francoeur, Nancy"'

1. Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation.

Author

Torre, Denis, Fstkchyan, Yesai, Ho, Jessica, Cheon, Youngseo, Patel, Roosheel, Degrace, Emma, Mzoughi, Slim, Schwarz, Megan, Mohammed, Kevin, Seo, Ji-Seon, Romero-Bueno, Raquel, Demircioglu, Deniz, Hasson, Dan, Tang, Weijing, Mahajani, Sameehan, Campisi, Laura, Zheng, Simin, Song, Won-Suk, Wang, Ying-Chih, Shah, Hardik, Francoeur, Nancy, Soto, Juan, Salfati, Zelda, Weirauch, Matthew, Warburton, Peter, Beaumont, Kristin, Smith, Melissa, Mulder, Lubbertus, Jang, Cholsoon, Lee, Daeyoup, De Rubeis, Silvia, Cobos, Inma, Tam, Oliver, Hammell, Molly, Seldin, Marcus, Sebra, Robert, Rosenberg, Brad, Benner, Chris, Guccione, Ernesto, Basu, Uttiya, Sebastiano, Vittorio, Shi, Yongsheng, Kessenbrock, Kai, Villalta, Sergio, Marazzi, Ivan, and Byun, Minji

Subjects
2CLC, Integrator, MERVL, RNA catabolism, elongation, endogenous retrovirus, non-coding RNA, stem cell, totipotent-like cells, transcription-associated RNA degradation, Endogenous Retroviruses, RNA, Nuclear, Epigenesis, Genetic, Heterochromatin, Gene Expression
Abstract

Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Published
2023

2. Isoform-resolved transcriptome of the human preimplantation embryo

Author

Torre, Denis, Francoeur, Nancy J, Kalma, Yael, Gross Carmel, Ilana, Melo, Betsaida S, Deikus, Gintaras, Allette, Kimaada, Flohr, Ron, Fridrikh, Maya, Vlachos, Konstantinos, Madrid, Kent, Shah, Hardik, Wang, Ying-Chih, Sridhar, Shwetha H, Smith, Melissa L, Eliyahu, Efrat, Azem, Foad, Amir, Hadar, Mayshar, Yoav, Marazzi, Ivan, Guccione, Ernesto, Schadt, Eric, Ben-Yosef, Dalit, and Sebra, Robert

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Reproductive Medicine, Pediatric, Biotechnology, Human Genome, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Humans, Transcriptome, Embryonic Development, Zygote, Gene Expression Profiling, Protein Isoforms, Sequence Analysis, RNA, Alternative Splicing, Blastocyst
Abstract

Human preimplantation development involves extensive remodeling of RNA expression and splicing. However, its transcriptome has been compiled using short-read sequencing data, which fails to capture most full-length mRNAs. Here, we generate an isoform-resolved transcriptome of early human development by performing long- and short-read RNA sequencing on 73 embryos spanning the zygote to blastocyst stages. We identify 110,212 unannotated isoforms transcribed from known genes, including highly conserved protein-coding loci and key developmental regulators. We further identify 17,964 isoforms from 5,239 unannotated genes, which are largely non-coding, primate-specific, and highly associated with transposable elements. These isoforms are widely supported by the integration of published multi-omics datasets, including single-cell 8CLC and blastoid studies. Alternative splicing and gene co-expression network analyses further reveal that embryonic genome activation is associated with splicing disruption and transient upregulation of gene modules. Together, these findings show that the human embryo transcriptome is far more complex than currently known, and will act as a valuable resource to empower future studies exploring development.

Published
2023

4. Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Author

Thompson, Ryan C., Simons, Nicole W., Wilkins, Lillian, Cheng, Esther, Del Valle, Diane Marie, Hoffman, Gabriel E., Cervia, Carlo, Fennessy, Brian, Mouskas, Konstantinos, Francoeur, Nancy J., Johnson, Jessica S., Lepow, Lauren, Le Berichel, Jessica, Chang, Christie, Beckmann, Aviva G., Wang, Ying-chih, Nie, Kai, Zaki, Nicholas, Tuballes, Kevin, Barcessat, Vanessa, Cedillo, Mario A., Yuan, Dan, Huckins, Laura, Roussos, Panos, Marron, Thomas U., Glicksberg, Benjamin S., Nadkarni, Girish, Heath, James R., Gonzalez-Kozlova, Edgar, Boyman, Onur, Kim-Schulze, Seunghee, Sebra, Robert, Merad, Miriam, Gnjatic, Sacha, Schadt, Eric E., Charney, Alexander W., and Beckmann, Noam D.

Published
2023
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5. Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection

Author

Wong Fok Lung, Tania, Charytonowicz, Daniel, Beaumont, Kristin G., Shah, Shivang S., Sridhar, Shwetha H., Gorrie, Claire L., Mu, Andre, Hofstaedter, Casey E., Varisco, David, McConville, Thomas H., Drikic, Marija, Fowler, Brandon, Urso, Andreacarola, Shi, Wei, Fucich, Dario, Annavajhala, Medini K., Khan, Ibrahim N., Oussenko, Irina, Francoeur, Nancy, Smith, Melissa L., Stockwell, Brent R., Lewis, Ian A., Hachani, Abderrahman, Upadhyay Baskota, Swikrity, Uhlemann, Anne-Catrin, Ahn, Danielle, Ernst, Robert K., Howden, Benjamin P., Sebra, Robert, and Prince, Alice

Published
2022
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6. Transcriptome and epigenome landscape of human cortical development modeled in organoids

Author

Amiri, Anahita, Coppola, Gianfilippo, Scuderi, Soraya, Wu, Feinan, Roychowdhury, Tanmoy, Liu, Fuchen, Pochareddy, Sirisha, Shin, Yurae, Safi, Alexias, Song, Lingyun, Zhu, Ying, Sousa, André MM, Gerstein, Mark, Crawford, Gregory E, Sestan, Nenad, Abyzov, Alexej, Vaccarino, Flora M, Akbarian, Schahram, An, Joon-Yong, Armoskus, Christoper, Ashley-Koch, Allison E, Beach, Thomas G, Belmont, Judson, Bendl, Jaroslav, Borrman, Tyler, Brown, Leanne, Brown, Miguel, Brown, Mimi, Brunetti, Tonya, Bryois, Julien, Burke, Emily E, Camarena, Adrian, Carlyle, Becky C, Chae, Yooree, Charney, Alexander W, Chen, Chao, Cheng, Lijun, Cherskov, Adriana, Choi, Jinmyung, Clarke, Declan, Collado-Torres, Leonardo, Dai, Rujia, De La Torre Ubieta, Luis, DelValle, Diane, Devillers, Olivia, Dracheva, Stella, Emani, Prashant S, Evgrafov, Oleg V, Farnham, Peggy J, Fitzgerald, Dominic, Flatow, Elie, Francoeur, Nancy, Fullard, John F, Gandal, Michael J, Gao, Tianliuyun, Garrett, Melanie E, Geschwind, Daniel H, Giase, Gina, Girdhar, Kiran, Giusti-Rodriguez, Paola, Goes, Fernando S, Goodman, Thomas, Grennan, Kay S, Gu, Mengting, Gürsoy, Gamze, Hadjimichael, Evi, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads E, Hoffman, Gabriel E, Huey, Jack, Hyde, Thomas M, Ivanov, Nikolay A, Jacobov, Rivka, Jaffe, Andrew E, Jiang, Yan, Jiang, Yi, Johnson, Graham D, Kassim, Bibi S, Kefi, Amira, Kim, Yunjung, Kitchen, Robert R, Kleiman, Joel E, Knowles, James A, Kozlenkov, Alexey, Li, Mingfeng, Li, Zhen, Lipska, Barbara K, Liu, Chunyu, Liu, Shuang, Mangravite, Lara M, Mariani, Jessica, Mattei, Eugenio, Miller, Daniel J, Moore, Jill, Nairn, Angus C, Navarro, Fabio CP, Park, Royce B, Peters, Mette A, and Pinto, Dalila

Subjects
Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Embryonic - Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Human Genome, Intellectual and Developmental Disabilities (IDD), Autism, Brain Disorders, Biotechnology, Clinical Research, Mental Health, Pediatric, Neurosciences, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Neurological, Cerebral Cortex, Enhancer Elements, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells, Models, Neurological, Neurogenesis, Organoids, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

Published
2018

7. Comprehensive functional genomic resource and integrative model for the human brain

Author

Wang, Daifeng, Liu, Shuang, Warrell, Jonathan, Won, Hyejung, Shi, Xu, Navarro, Fabio CP, Clarke, Declan, Gu, Mengting, Emani, Prashant, Yang, Yucheng T, Xu, Min, Gandal, Michael J, Lou, Shaoke, Zhang, Jing, Park, Jonathan J, Yan, Chengfei, Rhie, Suhn Kyong, Manakongtreecheep, Kasidet, Zhou, Holly, Nathan, Aparna, Peters, Mette, Mattei, Eugenio, Fitzgerald, Dominic, Brunetti, Tonya, Moore, Jill, Jiang, Yan, Girdhar, Kiran, Hoffman, Gabriel E, Kalayci, Selim, Gümüş, Zeynep H, Crawford, Gregory E, Roussos, Panos, Akbarian, Schahram, Jaffe, Andrew E, White, Kevin P, Weng, Zhiping, Sestan, Nenad, Geschwind, Daniel H, Knowles, James A, Gerstein, Mark B, Ashley-Koch, Allison E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, Belmont, Judson, DelValle, Diane, Francoeur, Nancy, Hadjimichael, Evi, Pinto, Dalila, van Bakel, Harm, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Peters, Mette A, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Chen, Chao, and Jiang, Yi

Subjects
Human Genome, Biotechnology, Schizophrenia, Mental Health, Brain Disorders, Genetics, Neurosciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Mental health, Brain, Datasets as Topic, Deep Learning, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Gene Expression Regulation, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Mental Disorders, Quantitative Trait Loci, Single-Cell Analysis, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

Published
2018

8. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Author

Gandal, Michael J, Zhang, Pan, Hadjimichael, Evi, Walker, Rebecca L, Chen, Chao, Liu, Shuang, Won, Hyejung, van Bakel, Harm, Varghese, Merina, Wang, Yongjun, Shieh, Annie W, Haney, Jillian, Parhami, Sepideh, Belmont, Judson, Kim, Minsoo, Moran Losada, Patricia, Khan, Zenab, Mleczko, Justyna, Xia, Yan, Dai, Rujia, Wang, Daifeng, Yang, Yucheng T, Xu, Min, Fish, Kenneth, Hof, Patrick R, Warrell, Jonathan, Fitzgerald, Dominic, White, Kevin, Jaffe, Andrew E, Peters, Mette A, Gerstein, Mark, Liu, Chunyu, Iakoucheva, Lilia M, Pinto, Dalila, Geschwind, Daniel H, Ashley-Koch, Allison E, Crawford, Gregory E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Akbarian, Schahram, Girdhar, Kiran, Jiang, Yan, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Hoffman, Gabriel E, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, DelValle, Diane, Francoeur, Nancy, Roussos, Panos, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Jiang, Yi, and Grennan, Kay S

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Mental Health, Intellectual and Developmental Disabilities (IDD), Neurosciences, Mental Illness, Human Genome, Schizophrenia, Biotechnology, Serious Mental Illness, Autism, Brain Disorders, Bipolar Disorder, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Mental health, Good Health and Well Being, Autism Spectrum Disorder, Brain, Genetic Predisposition to Disease, Humans, Protein Isoforms, RNA Splicing, Sequence Analysis, RNA, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Published
2018

10. Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression

Author

El Jamal, Siraj M., Pujadas, Elisabet, Ramos, Irene, Bryce, Clare, Grimes, Zachary M., Amanat, Fatima, Tsankova, Nadejda M., Mussa, Zarmeen, Olson, Sara, Salem, Fadi, Miorin, Lisa, Aydillo, Teresa, Schotsaert, Michael, Albrecht, Randy A., Liu, Wen-Chun, Marjanovic, Nada, Francoeur, Nancy, Sebra, Robert, Sealfon, Stuart C., García-Sastre, Adolfo, Fowkes, Mary, Cordon-Cardo, Carlos, and Westra, William H.

Published
2021
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11. Dietary fructose improves intestinal cell survival and nutrient absorption

Author

Taylor, Samuel R., Ramsamooj, Shakti, Liang, Roger J., Katti, Alyna, Pozovskiy, Rita, Vasan, Neil, Hwang, Seo-Kyoung, Nahiyaan, Navid, Francoeur, Nancy J., Schatoff, Emma M., Johnson, Jared L., Shah, Manish A., Dannenberg, Andrew J., Sebra, Robert P., Dow, Lukas E., Cantley, Lewis C., Rhee, Kyu Y., and Goncalves, Marcus D.

Published
2021
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12. The PsychENCODE project

Author

Akbarian, Schahram, Liu, Chunyu, Knowles, James A, Vaccarino, Flora M, Farnham, Peggy J, Crawford, Gregory E, Jaffe, Andrew E, Pinto, Dalila, Dracheva, Stella, Geschwind, Daniel H, Mill, Jonathan, Nairn, Angus C, Abyzov, Alexej, Pochareddy, Sirisha, Prabhakar, Shyam, Weissman, Sherman, Sullivan, Patrick F, State, Matthew W, Weng, Zhiping, Peters, Mette A, White, Kevin P, Gerstein, Mark B, Amiri, Anahita, Armoskus, Chris, Ashley-Koch, Allison E, Bae, Taejeong, Beckel-Mitchener, Andrea, Berman, Benjamin P, Coetzee, Gerhard A, Coppola, Gianfilippo, Francoeur, Nancy, Fromer, Menachem, Gao, Robert, Grennan, Kay, Herstein, Jennifer, Kavanagh, David H, Ivanov, Nikolay A, Jiang, Yan, Kitchen, Robert R, Kozlenkov, Alexey, Kundakovic, Marija, Li, Mingfeng, Li, Zhen, Liu, Shuang, Mangravite, Lara M, Mattei, Eugenio, Markenscoff-Papadimitriou, Eirene, Navarro, Fábio CP, North, Nicole, Omberg, Larsson, Panchision, David, Parikshak, Neelroop, Poschmann, Jeremie, Price, Amanda J, Purcaro, Michael, Reddy, Timothy E, Roussos, Panos, Schreiner, Shannon, Scuderi, Soraya, Sebra, Robert, Shibata, Mikihito, Shieh, Annie W, Skarica, Mario, Sun, Wenjie, Swarup, Vivek, Thomas, Amber, Tsuji, Junko, van Bakel, Harm, Wang, Daifeng, Wang, Yongjun, Wang, Kai, Werling, Donna M, Willsey, A Jeremy, Witt, Heather, Won, Hyejung, Wong, Chloe CY, Wray, Gregory A, Wu, Emily Y, Xu, Xuming, Yao, Lijing, Senthil, Geetha, Lehner, Thomas, Sklar, Pamela, and Sestan, Nenad

Subjects
Biotechnology, Human Genome, Brain Disorders, Genetics, Mental Health, Serious Mental Illness, Neurosciences, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Autism, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, Mental health, Animals, Brain, Chromosome Mapping, Epigenesis, Genetic, Genetic Code, Humans, Mental Disorders, Transcriptome, PsychENCODE Consortium, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE.

Published
2015

13. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Author

Beckmann, Noam D., Comella, Phillip H., Cheng, Esther, Lepow, Lauren, Beckmann, Aviva G., Tyler, Scott R., Mouskas, Konstantinos, Simons, Nicole W., Hoffman, Gabriel E., Francoeur, Nancy J., Del Valle, Diane Marie, Kang, Gurpawan, Do, Anh, Moya, Emily, Wilkins, Lillian, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Yi, Nancy, Yu, Alex, Chung, Jonathan, Hartnett, Matthew, Eaton, Melody, Hatem, Sandra, Jamal, Hajra, Akyatan, Alara, Tabachnikova, Alexandra, Liharska, Lora E., Cotter, Liam, Fennessy, Brian, Vaid, Akhil, Barturen, Guillermo, Shah, Hardik, Wang, Ying-chih, Sridhar, Shwetha Hara, Soto, Juan, Bose, Swaroop, Madrid, Kent, Ellis, Ethan, Merzier, Elyze, Vlachos, Konstantinos, Fishman, Nataly, Tin, Manying, Smith, Melissa, Xie, Hui, Patel, Manishkumar, Nie, Kai, Argueta, Kimberly, Harris, Jocelyn, Karekar, Neha, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Tuballes, Kevin, Scott, Ieisha, Kumar, Arvind, Jaladanki, Suraj, Agashe, Charuta, Thompson, Ryan, Clark, Evan, Losic, Bojan, Peters, Lauren, Roussos, Panagiotis, Zhu, Jun, Wang, Wenhui, Kasarskis, Andrew, Glicksberg, Benjamin S., Nadkarni, Girish, Bogunovic, Dusan, Elaiho, Cordelia, Gangadharan, Sandeep, Ofori-Amanfo, George, Alesso-Carra, Kasey, Onel, Kenan, Wilson, Karen M., Argmann, Carmen, Bunyavanich, Supinda, Alarcón-Riquelme, Marta E., Marron, Thomas U., Rahman, Adeeb, Kim-Schulze, Seunghee, Gnjatic, Sacha, Gelb, Bruce D., Merad, Miriam, Sebra, Robert, Schadt, Eric E., and Charney, Alexander W.

Published
2021
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15. Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation

Author

Tomlinson, Kira L., Lung, Tania Wong Fok, Dach, Felix, Annavajhala, Medini K., Gabryszewski, Stanislaw J., Groves, Ryan A., Drikic, Marija, Francoeur, Nancy J., Sridhar, Shwetha H., Smith, Melissa L., Khanal, Sara, Britto, Clemente J., Sebra, Robert, Lewis, Ian, Uhlemann, Anne-Catrin, Kahl, Barbara C., Prince, Alice S., and Riquelme, Sebastián A.

Published
2021
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16. Neuronal impact of patient-specific aberrant NRXN1α splicing

Author

Flaherty, Erin, Zhu, Shijia, Barretto, Natalie, Cheng, Esther, Deans, P. J. Michael, Fernando, Michael B., Schrode, Nadine, Francoeur, Nancy, Antoine, Alesia, Alganem, Khaled, Halpern, Madeline, Deikus, Gintaras, Shah, Hardik, Fitzgerald, Megan, Ladran, Ian, Gochman, Peter, Rapoport, Judith, Tsankova, Nadejda M., McCullumsmith, Robert, Hoffman, Gabriel E., Sebra, Robert, Fang, Gang, and Brennand, Kristen J.

Published
2019
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17. Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome

Author

Girdhar, Kiran, Hoffman, Gabriel E., Jiang, Yan, Brown, Leanne, Kundakovic, Marija, Hauberg, Mads E., Francoeur, Nancy J., Wang, Ying-chih, Shah, Hardik, Kavanagh, David H., Zharovsky, Elizabeth, Jacobov, Rivka, Wiseman, Jennifer R., Park, Royce, Johnson, Jessica S., Kassim, Bibi S., Sloofman, Laura, Mattei, Eugenio, Weng, Zhiping, Sieberts, Solveig K., Peters, Mette A., Harris, Brent T., Lipska, Barbara K., Sklar, Pamela, Roussos, Panos, and Akbarian, Schahram

Published
2018
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18. FLAIRR-Seq: A Method for Single-Molecule Resolution of Near Full-Length Antibody H Chain Repertoires

Author

Ford, Easton E., primary, Tieri, David, additional, Rodriguez, Oscar L., additional, Francoeur, Nancy J., additional, Soto, Juan, additional, Kos, Justin T., additional, Peres, Ayelet, additional, Gibson, William S., additional, Silver, Catherine A., additional, Deikus, Gintaras, additional, Hudson, Elizabeth, additional, Woolley, Cassandra R., additional, Beckmann, Noam, additional, Charney, Alexander, additional, Mitchell, Thomas C., additional, Yaari, Gur, additional, Sebra, Robert P., additional, Watson, Corey T., additional, and Smith, Melissa L., additional

Published
2023
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27. Bat pluripotent stem cells reveal unusual entanglement between host and viruses

Author

Déjosez, Marion, primary, Marin, Arturo, additional, Hughes, Graham M., additional, Morales, Ariadna E., additional, Godoy-Parejo, Carlos, additional, Gray, Jonathan L., additional, Qin, Yiren, additional, Singh, Arun A., additional, Xu, Hui, additional, Juste, Javier, additional, Ibáñez, Carlos, additional, White, Kris M., additional, Rosales, Romel, additional, Francoeur, Nancy J., additional, Sebra, Robert P., additional, Alcock, Dominic, additional, Volkert, Thomas L., additional, Puechmaille, Sébastien J., additional, Pastusiak, Andrzej, additional, Frost, Simon D.W., additional, Hiller, Michael, additional, Young, Richard A., additional, Teeling, Emma C., additional, García-Sastre, Adolfo, additional, and Zwaka, Thomas P., additional

Published
2023
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29. Bat pluripotent stem cells reveal unique entanglement between host and viruses

Author

Déjosez, Marion, primary, Marin, Arturo, additional, Hughes, Graham M., additional, Morales, Ariadna E., additional, Godoy-Parejo, Carlos, additional, Gray, Jonathan, additional, Qin, Yiren, additional, Singh, Arun A., additional, Xu, Hui, additional, Juste, Javier, additional, Ibáñez, Carlos, additional, White, Kris M., additional, Rosales, Romel, additional, Francoeur, Nancy J., additional, Sebra, Robert P., additional, Alcock, Dominic, additional, Puechmaille, Sébastien J., additional, Pastusiak, Andrzej, additional, Frost, Simon D.W., additional, Hiller, Michael, additional, Young, Richard A., additional, Teeling, Emma C., additional, García-Sastre, Adolfo, additional, and Zwaka, Thomas P., additional

Published
2022
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30. FLAIRR-seq: A novel method for single molecule resolution of near full-length immunoglobulin heavy chain repertoires

Author

Ford, Easton E., primary, Tieri, David, additional, Rodriguez, Oscar, additional, Francoeur, Nancy, additional, Soto, Juan, additional, Kos, Justin, additional, Peres, Ayelet, additional, Gibson, William, additional, Silver, Catherine A., additional, Deikus, Gintaras, additional, Hudson, Elizabeth, additional, Woolley, Cassandra R., additional, Beckmann, Noam, additional, Charney, Alexander, additional, Mitchell, Thomas C., additional, Yaari, Gur, additional, Sebra, Robert P., additional, Watson, Corey T., additional, and Smith, Melissa L., additional

Published
2022
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33. Bat pluripotent stem cells reveal unique entanglement between host and viruses

Author

Déjosez, Marion [0000-0002-1360-3260], Déjosez, Marion, Marin, Arturo, Hughes, Graham M., Morales, Ariadna E., Godoy-Parejo, Carlos, Gray, Jonathan, Qin, Yiren, Singh, Arun A., Xu, Hui, Juste, Javier, Ibáñez, Carlos, White, Kris M., Rosales, Romel, Francoeur, Nancy J., Sebra, Robert P., Alcock, Dominic, Puechmaille, Sébastien J., Pastusiak, Andrzej, Frost, Simon D. W., Hiller, Michael, Young, Richard A., Teeling, Emma C., García-Sastre, Adolfo, Zwaka, Tomas P., Déjosez, Marion [0000-0002-1360-3260], Déjosez, Marion, Marin, Arturo, Hughes, Graham M., Morales, Ariadna E., Godoy-Parejo, Carlos, Gray, Jonathan, Qin, Yiren, Singh, Arun A., Xu, Hui, Juste, Javier, Ibáñez, Carlos, White, Kris M., Rosales, Romel, Francoeur, Nancy J., Sebra, Robert P., Alcock, Dominic, Puechmaille, Sébastien J., Pastusiak, Andrzej, Frost, Simon D. W., Hiller, Michael, Young, Richard A., Teeling, Emma C., García-Sastre, Adolfo, and Zwaka, Tomas P.

Abstract

Bats have evolved features unique amongst mammals, including flight, laryngeal echolocation, and certain species have been shown to have a unique immune response that may enable them to tolerate viruses such as SARS-CoVs, MERS-CoVs, Nipah, and Marburg viruses. Robust cellular models have yet to be developed for bats, hindering our ability to further understand their special biology and handling of viral pathogens. To establish bats as new model study species, we generated induced pluripotent stem cells (iPSCs) from a wild greater horseshoe bat (Rhinolophus ferrumequinum) using a modified Yamanaka protocol. Rhinolophids are amongst the longest living bat species and are asymptomatic carriers of coronaviruses, including one of the viruses most closely related to SARS-CoV-2. Bat induced pluripotent stem (BiPS) cells were stable in culture, readily differentiated into all three germ layers, and formed complex embryoid bodies, including organoids. The BiPS cells were found to have a core pluripotency gene expression program similar to that of other species, but it also resembled that of cells attacked by viruses. The BiPS cells produced a rich set of diverse endogenized viral sequences and in particular retroviruses. We further validated our protocol by developing iPS cells from an evolutionary distant bat species Myotis myotis (greater mouse-eared bat) non-lethally sampled in the wild, which exhibited similar attributes to the greater horseshoe bat iPS cells, suggesting that this unique pluripotent state evolved in the ancestral bat lineage. Although previous studies have suggested that bats have developed powerful strategies to tame their inflammatory response, our results argue that they have also evolved mechanisms to accommodate a substantial load of endogenous viral sequences and suggest that the natural history of bats and viruses is more profoundly intertwined than previously thought. Further study of bat iPS cells and their differentiated progeny should advance

Published
2022

34. Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

Author

Sieberts, Solveig K., Perumal, Thanneer M., Carrasquillo, Minerva M., Allen, Mariet, Reddy, Joseph S., Hoffman, Gabriel E., Dang, Kristen K., Calley, John, Ebert, Philip J., Eddy, James, Wang, Xue, Greenwood, Anna K., Mostafavi, Sara, Akbarian, Schahram, Bendl, Jaroslav, Breen, Michael S., Brennand, Kristen, Brown, Leanne, Browne, Andrew, Buxbaum, Joseph D., Charney, Alexander, Chess, Andrew, Couto, Lizette, Crawford, Greg, Devillers, Olivia, Devlin, Bernie, Dobbyn, Amanda, Domenici, Enrico, Filosi, Michele, Flatow, Elie, Francoeur, Nancy, Fullard, John, Gil, Sergio Espeso, Girdhar, Kiran, Gulyás-Kovács, Attila, Gur, Raquel, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads Engel, Huckins, Laura, Jacobov, Rivky, Jiang, Yan, Johnson, Jessica S., Kassim, Bibi, Kim, Yungil, Klei, Lambertus, Kramer, Robin, Lauria, Mario, Lehner, Thomas, Lewis, David A., Lipska, Barbara K., Montgomery, Kelsey, Park, Royce, Rosenbluh, Chaggai, Roussos, Panagiotis, Ruderfer, Douglas M., Senthil, Geetha, Shah, Hardik R., Sloofman, Laura, Song, Lingyun, Stahl, Eli, Sullivan, Patrick, Visintainer, Roberto, Wang, Jiebiao, Wang, Ying-Chih, Wiseman, Jennifer, Xia, Eva, Zhang, Wen, Zharovsky, Elizabeth, Addis, Laura, Addo, Sadiya N., Airey, David Charles, Arnold, Matthias, Bennett, David A., Bi, Yingtao, Biber, Knut, Blach, Colette, Bradhsaw, Elizabeth, Brennan, Paul, Canet-Aviles, Rosa, Cao, Sherry, Cavalla, Anna, Chae, Yooree, Chen, William W., Cheng, Jie, Collier, David Andrew, Dage, Jeffrey L., Dammer, Eric B., Davis, Justin Wade, Davis, John, Drake, Derek, Duong, Duc, Eastwood, Brian J., Ehrlich, Michelle, Ellingson, Benjamin, Engelmann, Brett W., Esmaeelinieh, Sahar, Felsky, Daniel, Funk, Cory, Gaiteri, Chris, Gandy, Samuel, Gao, Fan, Gileadi, Opher, Golde, Todd, Grosskurth, Shaun E., Gupta, Rishi R., Gutteridge, Alex X., Hooli, Basavaraj, Humphryes-Kirilov, Neil, Iijima, Koichi, James, Corey, Jung, Paul M., Kaddurah-Daouk, Rima, Kastenmuller, Gabi, Klein, Hans-Ulrich, Kummer, Markus, Lacor, Pascale N., Lah, James, Laing, Emma, Levey, Allan, Li, Yupeng, Lipsky, Samantha, Liu, Yushi, Liu, Jimmy, Liu, Zhandong, Louie, Gregory, Lu, Tao, Ma, Yiyi, Matsuoka, Yasuji Y., Menon, Vilas, Miller, Bradley, Misko, Thomas P., Mollon, Jennifer E., Mukherjee, Sumit, Noggle, Scott, Pao, Ping-Chieh, Pearce, Tracy Young, Pearson, Neil, Penny, Michelle, Petyuk, Vladislav A., Price, Nathan, Quarless, Danjuma X., Ravikumar, Brinda, Ried, Janina S., Ruble, Cara Lee Ann, Runz, Heiko, Saykin, Andrew J., Schadt, Eric, Scherschel, James E., Seyfried, Nicholas, Shulman, Joshua M., Snyder, Phil, Soares, Holly, Srivastava, Gyan P., Stockmann, Henning, Taga, Mariko, Tasaki, Shinya, Tenenbaum, Jessie, Tsai, Li-Huei, Vasanthakumar, Aparna, Wachter, Astrid, Wang, Yaming, Wang, Hong, Wang, Minghui, Whelan, Christopher D., White, Charles, Woo, Kara H., Wren, Paul, Wu, Jessica W., Xi, Hualin S., Yankner, Bruce A., Younkin, Steven G., Yu, Lei, Zavodszky, Maria, Zhang, Wenling, Zhang, Guoqiang, Zhang, Bin, Zhu, Jun, Omberg, Larsson, Peters, Mette A., Logsdon, Benjamin A., De Jager, Philip L., Ertekin-Taner, Nilüfer, Mangravite, Lara M., Sieberts, Solveig K., Perumal, Thanneer M., Carrasquillo, Minerva M., Allen, Mariet, Reddy, Joseph S., Hoffman, Gabriel E., Dang, Kristen K., Calley, John, Ebert, Philip J., Eddy, James, Wang, Xue, Greenwood, Anna K., Mostafavi, Sara, Akbarian, Schahram, Bendl, Jaroslav, Breen, Michael S., Brennand, Kristen, Brown, Leanne, Browne, Andrew, Buxbaum, Joseph D., Charney, Alexander, Chess, Andrew, Couto, Lizette, Crawford, Greg, Devillers, Olivia, Devlin, Bernie, Dobbyn, Amanda, Domenici, Enrico, Filosi, Michele, Flatow, Elie, Francoeur, Nancy, Fullard, John, Gil, Sergio Espeso, Girdhar, Kiran, Gulyás-Kovács, Attila, Gur, Raquel, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads Engel, Huckins, Laura, Jacobov, Rivky, Jiang, Yan, Johnson, Jessica S., Kassim, Bibi, Kim, Yungil, Klei, Lambertus, Kramer, Robin, Lauria, Mario, Lehner, Thomas, Lewis, David A., Lipska, Barbara K., Montgomery, Kelsey, Park, Royce, Rosenbluh, Chaggai, Roussos, Panagiotis, Ruderfer, Douglas M., Senthil, Geetha, Shah, Hardik R., Sloofman, Laura, Song, Lingyun, Stahl, Eli, Sullivan, Patrick, Visintainer, Roberto, Wang, Jiebiao, Wang, Ying-Chih, Wiseman, Jennifer, Xia, Eva, Zhang, Wen, Zharovsky, Elizabeth, Addis, Laura, Addo, Sadiya N., Airey, David Charles, Arnold, Matthias, Bennett, David A., Bi, Yingtao, Biber, Knut, Blach, Colette, Bradhsaw, Elizabeth, Brennan, Paul, Canet-Aviles, Rosa, Cao, Sherry, Cavalla, Anna, Chae, Yooree, Chen, William W., Cheng, Jie, Collier, David Andrew, Dage, Jeffrey L., Dammer, Eric B., Davis, Justin Wade, Davis, John, Drake, Derek, Duong, Duc, Eastwood, Brian J., Ehrlich, Michelle, Ellingson, Benjamin, Engelmann, Brett W., Esmaeelinieh, Sahar, Felsky, Daniel, Funk, Cory, Gaiteri, Chris, Gandy, Samuel, Gao, Fan, Gileadi, Opher, Golde, Todd, Grosskurth, Shaun E., Gupta, Rishi R., Gutteridge, Alex X., Hooli, Basavaraj, Humphryes-Kirilov, Neil, Iijima, Koichi, James, Corey, Jung, Paul M., Kaddurah-Daouk, Rima, Kastenmuller, Gabi, Klein, Hans-Ulrich, Kummer, Markus, Lacor, Pascale N., Lah, James, Laing, Emma, Levey, Allan, Li, Yupeng, Lipsky, Samantha, Liu, Yushi, Liu, Jimmy, Liu, Zhandong, Louie, Gregory, Lu, Tao, Ma, Yiyi, Matsuoka, Yasuji Y., Menon, Vilas, Miller, Bradley, Misko, Thomas P., Mollon, Jennifer E., Mukherjee, Sumit, Noggle, Scott, Pao, Ping-Chieh, Pearce, Tracy Young, Pearson, Neil, Penny, Michelle, Petyuk, Vladislav A., Price, Nathan, Quarless, Danjuma X., Ravikumar, Brinda, Ried, Janina S., Ruble, Cara Lee Ann, Runz, Heiko, Saykin, Andrew J., Schadt, Eric, Scherschel, James E., Seyfried, Nicholas, Shulman, Joshua M., Snyder, Phil, Soares, Holly, Srivastava, Gyan P., Stockmann, Henning, Taga, Mariko, Tasaki, Shinya, Tenenbaum, Jessie, Tsai, Li-Huei, Vasanthakumar, Aparna, Wachter, Astrid, Wang, Yaming, Wang, Hong, Wang, Minghui, Whelan, Christopher D., White, Charles, Woo, Kara H., Wren, Paul, Wu, Jessica W., Xi, Hualin S., Yankner, Bruce A., Younkin, Steven G., Yu, Lei, Zavodszky, Maria, Zhang, Wenling, Zhang, Guoqiang, Zhang, Bin, Zhu, Jun, Omberg, Larsson, Peters, Mette A., Logsdon, Benjamin A., De Jager, Philip L., Ertekin-Taner, Nilüfer, and Mangravite, Lara M.

Abstract

© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).

Published
2022

35. Additional file 1 of LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer

Author

Sun, Zeguo, Zhang, Rui, Zhang, Xiao, Sun, Yifei, Liu, Pengpeng, Francoeur, Nancy, Han, Lei, Lam, Wan Yee, Yi, Zhengzi, Sebra, Robert, Walsh, Martin, Yu, Jinpu, and Zhang, Weijia

Abstract

Additional file 1. Figure S1. Validation of LCT activity in TJMUCH cohort.(A) Number of LCT events overlapped between TJMUCH cohort and TCGA LUSC cohort.(B) Comparison of overall methylation level between LUSC and LUAD patients fromTCGA. (C) Distribution of LCT event number in each sample. (D) Expression (readper mission) between tumor and control samples. (E) Frequency of the top 20 LCTevents (named by their target genes). (F) Enriched GO terms of the recurrentLCT affected genes (more than 2 samples). (G) Differentially expressed LCTsbetween tumor and normal samples. Left panel showing the number of samplesdetected with each LCT event and the right panel showing the expression ofcorresponding LCT event across samples (red represents tumor samples while bluerepresents normal samples). Figure S2. Association of LCT with Metabolic, Immuneprocess, Genomic Instability and Clinical States. (A) Enriched GO terms ofgenes positively or negatively co-expressed with overall LCT expression in eachsample. (B) The GSEA enrichment plot for meta-markers of each immune cell type.Genes are ranked by the fold change of expression in LCT-high samples (left)versus LCT-low samples (right) (C) Correlation of methylation level and CNVlevel with overall LCT activity in each sample. (D) Comparison of LCTexpression in different cancer stages and TMB quartiles. (E) Differentiallyexpressed LCT events (named by targeted gene), which are highly expressed intumor than control. Left panel shows the number of samples containing the LCT eventwhile right panel shows the expression of LCT events among all the samples,grouped by tumor (red) and normal control (blue). (F) Survival curve ofpatients grouped as L1-high and L1-low by the total expression of survivalrelated LCTs. Figure S3. Validation of the association of overall LCTactivity and Immune function in TJMUCH cohort. (A) Enriched GO terms of thegenes positively co-expressed with overall LCT activity. (B) Enriched GO termsof the genes negatively co-expressed with LCT activity. (C) GSEA analysis ofthe immune markers enrichment in LCT-high versus LCT-low samples. Figure S4. LCT activity in tumor cells. (A) Frequencyof overlapped LCT between bulk and single cell data sets. Left panel shows thefrequency of each LCT event in each cancer type from TCGA bulk sequencing.Right panel shows the occurrence of each LCT event in each sample from singlecell data set. (B) Umap of cells colored by individual. (C) Markers for annotationof each cell type. (D) the proportion of each cell type in each sample. Figure S5. LCT related DEGs between cellpopulation. (A) Umap and trajectory of tumor cells fromPatient1, Patient2 and Patient5. Cells detected with LCT events were coloredred. (B) DEGs between LCT enriched tumor subtype versus other tumor cells. (C)DEGs between LCT positive tumor cells versus LCT negative tumor cells in LCTenriched tumor subtype. FigureS6. The mitochondrialmorphology and functions. (A) The TEM results of H520OV-CTRL, H520OV-L1-FGGY, and BEAS-2B. (B) The OCR and ECAR results ofH520OV-CTRLand H520OV-L1-FGGY. (C) The MMP results of H520OV-CTRLand H520OV-L1-FGGY.(D) The ATP productionof H520OV-CTRLand H520OV-L1-FGGY. Figure S7. The oncogenic roles of L1-FGGY/12-LOX/GPR31in SK-MES-1 cells. (A) The relative RNA expression of 12-LOX and 15-LOXdetected in SK-MES-1OV-CTRL and SK-MES-1OV-L1-FGGY, as well as in SK-MES-1OV-L1-FGGY treated with either ML355 or PD146176. (B) The secretionvalue of 12S-HETE and 15S-HETE detected in SK-MES-1OV-CTRL, SK-MES-1OV-L1-FGGY, and SK-MES-1OV-L1-FGGY treated with either ML355or PD146176. (C) The proliferation of SK-MES-1OV-CTRL, SK-MES-1OV-L1-FGGY, SK-MES-1OV-L1-FGGY+sh-GPR31, and SK-MES-1OV-L1-FGGY treated with either ML355 or PD146176 was detectedusing CCK8 method. (D) The statistical results of migration rates of SK-MES-1OV-CTRL,SK-MES-1OV-L1-FGGY,SK-MES-1OV-L1-FGGY+sh-GPR31, and SK-MES-1OV-L1-FGGY treated with either ML355or PD146176 in wound healing assays. (E) The statistical results of invasionnumber of SK-MES-1OV-CTRL, SK-MES-1OV-L1-FGGY, SK-MES-1OV-L1-FGGY+sh-GPR31, and SK-MES-1OV-L1-FGGY treated with either ML355or PD146176 in trans-well invasion assays. The data are shown as mean ± SD withplots. * and ** indicate p

Published
2022
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38. Identification of Alternative Polyadenylation in Cyanidioschyzon merolae Through Long-Read Sequencing of mRNA

Author

Schärfen, Leonard, primary, Zigackova, Dagmar, additional, Reimer, Kirsten A., additional, Stark, Martha R., additional, Slat, Viktor A., additional, Francoeur, Nancy J., additional, Wells, Melissa L., additional, Zhou, Lecong, additional, Blackshear, Perry J., additional, Neugebauer, Karla M., additional, and Rader, Stephen D., additional

Published
2022
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39. Cell-specific histone modification maps link schizophrenia risk to the neuronal epigenome

Author

Girdhar, Kiran, Hoffman, Gabriel E., Jiang, Yan, Brown, Leanne, Kundakovic, Marija, Hauberg, Mads E., Francoeur, Nancy J., Wang, Ying-chih, Shah, Hardik, Kavanagh, David H., Zharovsky, Elizabeth, Jacobov, Rivka, Wiseman, Jennifer R., Park, Royce, Johnson, Jessica S., Kassim, Bibi S., Sloofman, Laura, Mattei, Eugenio, Weng, Zhiping, Sieberts, Solveig K., Peters, Mette A., Harris, Brent T., Lipska, Barbara K., Sklar, Pamela, Roussos, Panos, and Akbarian, Schahram

Subjects
Risk, Brain Mapping, Neurotic Disorders, Depression, Genetic Variation, Prefrontal Cortex, Gyrus Cinguli, Article, Chromatin, Epigenesis, Genetic, Frontal Lobe, Histones, Alzheimer Disease, Schizophrenia, Educational Status, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical areas implicated in psychosis, dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuronal-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-lysine 4 (H3K4me3) and H3-acetyl-lysine 27 (H3K27ac). Differences between neuronal and neuronal-depleted chromatin states were the major axis of variation in histone modification profiles followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci (hQTLs) were identified in neuronal and neuronal-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly overrepresented in neuronal H3K4me3 and H3K27ac landscapes. Our PsychENCODE and CommonMind sponsored resource highlights the critical role of cell-type specific signatures at regulatory and disease-associated non-coding sequences in the human frontal lobe.

Published
2018

40. Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms

Author

Pujadas, Elisabet, primary, Beaumont, Michael, additional, Shah, Hardik, additional, Schrode, Nadine, additional, Francoeur, Nancy, additional, Shroff, Sanjana, additional, Bryce, Clare, additional, Grimes, Zachary, additional, Gregory, Jill, additional, Donnelly, Ryan, additional, Fowkes, Mary E., additional, Beaumont, Kristin, additional, Sebra, Robert, additional, and Cordon-Cardo, Carlos, additional

Published
2021
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42. Introductions and early spread of SARS-CoV-2 in the New York City area

Author

Gonzalez-Reiche, Ana S., primary, Hernandez, Matthew M., additional, Sullivan, Mitchell J., additional, Ciferri, Brianne, additional, Alshammary, Hala, additional, Obla, Ajay, additional, Fabre, Shelcie, additional, Kleiner, Giulio, additional, Polanco, Jose, additional, Khan, Zenab, additional, Alburquerque, Bremy, additional, van de Guchte, Adriana, additional, Dutta, Jayeeta, additional, Francoeur, Nancy, additional, Melo, Betsaida Salom, additional, Oussenko, Irina, additional, Deikus, Gintaras, additional, Soto, Juan, additional, Sridhar, Shwetha Hara, additional, Wang, Ying-Chih, additional, Twyman, Kathryn, additional, Kasarskis, Andrew, additional, Altman, Deena R., additional, Smith, Melissa, additional, Sebra, Robert, additional, Aberg, Judith, additional, Krammer, Florian, additional, García-Sastre, Adolfo, additional, Luksza, Marta, additional, Patel, Gopi, additional, Paniz-Mondolfi, Alberto, additional, Gitman, Melissa, additional, Sordillo, Emilia Mia, additional, Simon, Viviana, additional, and van Bakel, Harm, additional

Published
2020
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43. Recurrent IDH mutations in high-grade meningioma

Author

Gill, Corey M, primary, Loewenstern, Joshua, primary, Rutland, John W, primary, Arib, Hanane, primary, Francoeur, Nancy, primary, Wang, Ying-Chih, primary, Fishman, Nataly, primary, Pain, Margaret, primary, Umphlett, Melissa, primary, Kinoshita, Yayoi, primary, McBride, Russell B, primary, Bederson, Joshua, primary, Donovan, Michael, primary, Smith, Melissa, primary, Sebra, Robert, primary, Shrivastava, Raj K, primary, and Fowkes, Mary, primary

Published
2020
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46. Sampling the host response to SARS-CoV-2 in hospitals under siege

Author

Charney, Alexander W., Simons, Nicole W., Mouskas, Konstantinos, Lepow, Lauren, Cheng, Esther, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Del Valle, Diane Marie, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Patel, Manishkumar, Xie, Hui, Yi, Nancy, Yu, Alex, Kang, Gurpawan, Mendoza, Anthony, Liharska, Lora E., Moya, Emily, Hartnett, Matthew, Hatem, Sandra, Wilkins, Lillian, Eaton, Melody, Jamal, Hajra, Tuballes, Kevin, Chen, Steven T., Tabachnikova, Alexandra, Chung, Jonathan, Harris, Jocelyn, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Argueta, Kimberly, Karekar, Neha, Lee, Brian, Kelly, Geoffrey, Geanon, Daniel, Handler, Diana, Leech, John, Stefanos, Hiyab, Dawson, Travis, Scott, Ieisha, Francoeur, Nancy, Johnson, Jessica S., Vaid, Akhil, Glicksberg, Benjamin S., Nadkarni, Girish N., Schadt, Eric E., Gelb, Bruce D., Rahman, Adeeb, Sebra, Robert, Martin, Glenn, Agashe, Charuta, Agrawal, Priyal, Akyatan, Alara, Alesso-Carra, Kasey, Alibo, Eziwoma, Alvarez, Kelvin, Amabile, Angelo, Ascolillo, Steven, Bailey, Rasheed, Begani, Priya, Correra, Paloma Bravo, Brown, Stacey-Ann, Buckup, Mark, Burka, Larissa, Cambron, Lena, Carrara, Gina, Chang, Serena, Chien, Jonathan, Chowdhury, Mashkura, Bozkus, Cansu Cimen, Comella, Phillip, Cosgrove, Dana, Cossarini, Francesca, Cotter, Liam, Dave, Arpit, Dayal, Bheesham, Dhainaut, Maxime, Dornfeld, Rebecca, Dul, Katie, Eber, Nissan, Elaiho, Cordelia, Fabris, Frank, Faith, Jeremiah, Falci, Dominique, Feng, Susie, Fennessy, Brian, Fernandes, Marie, Gangadharan, Sandeep, Grabowska, Joanna, Gyimesi, Gavin, Hamdani, Maha, Herbinet, Manon, Herrera, Elva, Hochman, Arielle, Hoffman, Gabriel E., Hook, Jaime, Horta, Laila, Humblin, Etienne, Karim, Subha, Kim, Jessica, Lebovitch, Dannielle, Lee, Grace, Lee, Gyu Ho, Lee, Jacky, Leventhal, Mike, Lindblad, Katherine, Livanos, Alexandra, Machado, Rosalie, Mahmood, Zafar, Mar, Kelcey, Maskey, Shrisha, Matthews, Paul, Meckel, Katherine, Mehandru, Saurabh, Mercedes, Cynthia, Meyer, Dara, Mollaoglu, Gurkan, Morris, Sarah, Nie, Kai, Nisenholtz, Marjorie, Ofori-Amanfo, George, Onel, Kenan, Ounadjela, Merouane, Patel, Vishwendra, Pruitt, Cassandra, Rathi, Shivani, Redes, Jamie, Reyes-Torres, Ivan, Rodrigues, Alcina, Rodriguez, Alfonso, Roudko, Vladimir, Ruiz, Evelyn, Scalzo, Pearl, Silva, Pedro, Schanoski, Alessandra Soares, Straw, Meghan, Tabachnikova, Sasha, Teague, Collin, Upadhyaya, Bhaskar, Van Der Heide, Verena, Vaninov, Natalie, Wacker, Daniel, Walsh, Hadley, Wilk, C. Matthias, Wilson, Jessica, Wilson, Karen M., Xue, Li, Yeboah, Naa-akomaah, Young, Sabina, Zaks, Nina, Zha, Renyuan, Marron, Thomas, Beckmann, Noam, Kim-Schulze, Seunghee, Gnjatic, Sacha, and Merad, Miriam

Subjects
Siege, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Host response, Sampling (statistics), General Medicine, biology.organism_classification, Virology, General Biochemistry, Genetics and Molecular Biology, Pandemic, Medicine, business, Betacoronavirus
Published
2020
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47. A microRNA activity map of human mesenchymal tumors: connections to oncogenic pathways; an integrative transcriptomic study

Author

Fountzilas Elena, Kelly Andrew D, Perez-Atayde Antonio R, Goldsmith Jeffrey, Konstantinopoulos Panagiotis A, Francoeur Nancy, Correll Mick, Rubio Renee, Hu Lan, Gebhardt Mark C, Quackenbush John, and Spentzos Dimitrios

Subjects
MicroRNA, Microarray, RAS, Mesenchymal tumors, MicroRNA biogenesis, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background MicroRNAs (miRNAs) are nucleic acid regulators of many human mRNAs, and are associated with many tumorigenic processes. miRNA expression levels have been used in profiling studies, but some evidence suggests that expression levels do not fully capture miRNA regulatory activity. In this study we integrate multiple gene expression datasets to determine miRNA activity patterns associated with cancer phenotypes and oncogenic pathways in mesenchymal tumors – a very heterogeneous class of malignancies. Results Using a computational method, we identified differentially activated miRNAs between 77 normal tissue specimens and 135 sarcomas and we validated many of these findings with microarray interrogation of an independent, paraffin-based cohort of 18 tumors. We also showed that miRNA activity is imperfectly correlated with miRNA expression levels. Using next-generation miRNA sequencing we identified potential base sequence alterations which may explain differential activity. We then analyzed miRNA activity changes related to the RAS-pathway and found 21 miRNAs that switch from silenced to activated status in parallel with RAS activation. Importantly, nearly half of these 21 miRNAs were predicted to regulate integral parts of the miRNA processing machinery, and our gene expression analysis revealed significant reductions of these transcripts in RAS-active tumors. These results suggest an association between RAS signaling and miRNA processing in which miRNAs may attenuate their own biogenesis. Conclusions Our study represents the first gene expression-based investigation of miRNA regulatory activity in human sarcomas, and our findings indicate that miRNA activity patterns derived from integrated transcriptomic data are reproducible and biologically informative in cancer. We identified an association between RAS signaling and miRNA processing, and demonstrated sequence alterations as plausible causes for differential miRNA activity. Finally, our study highlights the value of systems level integrative miRNA/mRNA assessment with high-throughput genomic data, and the applicability of paraffin-tissue-derived RNA for validation of novel findings.

Published
2012
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48. Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Author

Thompson, Ryan C., Simons, Nicole W., Wilkins, Lillian, Cheng, Esther, Del Valle, Diane Marie, Hoffman, Gabriel E., Cervia, Carlo, Fennessy, Brian, Mouskas, Konstantinos, Francoeur, Nancy J., Johnson, Jessica S., Lepow, Lauren, Le Berichel, Jessica, Chang, Christie, Beckmann, Aviva G., Wang, Ying-chih, Nie, Kai, Zaki, Nicholas, Tuballes, Kevin, Barcessat, Vanessa, Cedillo, Mario A., Yuan, Dan, Huckins, Laura, Roussos, Panos, Marron, Thomas U., Glicksberg, Benjamin S., Nadkarni, Girish, Heath, James R., Gonzalez-Kozlova, Edgar, Boyman, Onur, Kim-Schulze, Seunghee, Sebra, Robert, Merad, Miriam, Gnjatic, Sacha, Schadt, Eric E., Charney, Alexander W., and Beckmann, Noam D.

Abstract

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.

Published
2022
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50. The PsychENCODE project

Author

Weissman, Sherman, Geschwind, Daniel H, Gerstein, Mark B, Farnham, Peggy J, Akbarian, Schahram, Nairn, Angus C, Armoskus, Chris, Dracheva, Stella, Mill, Jonathan, Sullivan, Patrick F, Vaccarino, Flora M, Coetzee, Gerhard A, Jaffe, Andrew E, Pochareddy, Sirisha, Abyzov, Alexej, Amiri, Anahita, Ashley-Koch, Allison E, Pinto, Dalila, White, Kevin P, Beckel-Mitchener, Andrea, Coppola, Gianfilippo, Knowles, James A, Francoeur, Nancy, Peters, Mette A, Crawford, Gregory E, Berman, Benjamin P, Weng, Zhiping, Prabhakar, Shyam, Bae, Taejeong, Fromer, Menachem, Liu, Chunyu, and State, Matthew W

Abstract

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE.

Published
2015
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