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1. Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study

Author

Schlapbach, Luregn J, Ganesamoorthy, Devika, Wilson, Clare, Raman, Sainath, George, Shane, Snelling, Peter J, Phillips, Natalie, Irwin, Adam, Sharp, Natalie, Le Marsney, Renate, Chavan, Arjun, Hempenstall, Allison, Bialasiewicz, Seweryn, MacDonald, Anna D, Grimwood, Keith, Kling, Jessica C, McPherson, Stephen J, Blumenthal, Antje, Kaforou, Myrsini, Levin, Michael, Herberg, Jethro A, Gibbons, Kristen S, Coin, Lachlan J M, Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stephanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Shailes, Hannah, Thakker, Clare, Bokhandi, S., Power, Sue, Barham, Heather, Pathan, N., Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S., Patel, S., McCorkell, Jenni, Davies, P., Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R., Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C., White, Sonia, Fortune, Peter-Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriaga, Antonio, Fernández, Sonia Serén, del Sol Porto Silva, María, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, Cruz León León, María, Navarro Mingorance, Álvaro, Gabaldó Barrio, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Contreras, J. Ruiz, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, José Lozano, María, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, Mª del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, R., Tutu van Furth, A.M., van der Flier, M., Boeddha, N.P., Driessen, G.J.A., Emonts, M., Hazelzet, J.A., Kuijpers, T.W., Pajkrt, D., Sanders, E.A.M., van de Beek, D., van der Ende, A., Philipsen, H.L.A., Adeel, A.O.A., Breukels, M.A., Brinkman, D.M.C., de Korte, C.C.M.M., de Vries, E., de Waal, W.J., Dekkers, R., Dings-Lammertink, A., Doedens, R.A., Donker, A.E., Dousma, M., Faber, T.E., Gerrits, G.P.J.M., Gerver, J.A.M., Heidema, J., Homan-van der Veen, J., Jacobs, M.A.M., Jansen, N.J.G., Kawczynski, P., Klucovska, K., Kneyber, M.C.J., Koopman-Keemink, Y., Langenhorst, V.J., Leusink, J., Loza, B.F., Merth, I.T., Miedema, C.J., Neeleman, C., Noordzij, J.G., Obihara, C.C., van Overbeek- van Gils, A.L.T., Poortman, G.H., Potgieter, S.T., Potjewijd, J., Rosias, P.P.R., Sprong, T., ten Tussher, G.W., Thio, B.J., Tramper-Stranders, G.A., van Deuren, M., van der Meer, H., van Kuppevelt, A.J.M., van Wermeskerken, A.M., Verwijs, W.A., Wolfs, T.F.W., Schlapbach, Luregn J., Agyeman, Philipp, Aebi, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan D., Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel, Anderson, Suzanne, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Kohlfürst, Daniela S., Binder, Alexander, Schweintzger, Nina A., Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Žukovskaja, Veslava, Hibberd, Martin L., Davila, Sonia, Delany, Isabel, Schlapbach, Luregn J, Raman, Sainath, Sharp, Nathalie, Phillips, Natalie, Irwin, Adam, Balch, Ross, Harley, Amanda, Johnson, Kerry, Sever, Zoe, George, Shane, Grimwood, Keith, Snelling, Peter J, Chavan, Arjun, Kitcatt, Eleanor, Lawton, Luke, Hempenstall, Allison, Pilot, Pelista, Gibbons, Kristen S, Le Marsney, Renate, Blumenthal, Antje, Ganesamoorthy, Devika, Pardo, Carolyn, Kling, Jessica, McPherson, Stephen, MacDonald, Anna D, Bialasiewicz, Seweryn, Pham, Trang, and Coin, Lachlan

Abstract

Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection.

Published
2024
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2. Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases

Author

Yeoh, Sophya, Estrada-Rivadeneyra, Diego, Jackson, Heather, Keren, Ilana, Galassini, Rachel, Cooray, Samantha, Shah, Priyen, Agyeman, Philipp, Basmaci, Romain, Carrol, Enitan, Emonts, Marieke, Fink, Colin, Kuijpers, Taco, Martinon-Torres, Federico, Mommert-Tripon, Marine, Paulus, Stephane, Pokorn, Marko, Rojo, Pablo, Romani, Lorenza, Schlapbach, Luregn, Schweintzger, Nina, Shen, Ching-Fen, Tsolia, Maria, Usuf, Effua, van der Flier, Michiel, Vermont, Clementien, von Both, Ulrich, Yeung, Shunmay, Zavadska, Dace, Coin, Lachlan, Cunnington, Aubrey, Herberg, Jethro, Levin, Michael, Kaforou, Myrsini, and Hamilton, Shea

Published
2024
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3. A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study

Author

Jackson, Heather R, Zandstra, Judith, Menikou, Stephanie, Hamilton, Melissa Shea, McArdle, Andrew J, Fischer, Roman, Thorne, Adam M, Huang, Honglei, Tanck, Michael W, Jansen, Machiel H, De, Tisham, Agyeman, Philipp K A, Von Both, Ulrich, Carrol, Enitan D, Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, Gloerich, Jolein, De Groot, Ronald, Moll, Henriette A, Pokorn, Marko, Pollard, Andrew J, Schlapbach, Luregn J, Tsolia, Maria N, Usuf, Effua, Wright, Victoria J, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J M, Casals-Pascual, Climent, Cunnington, Aubrey J, Martinon-Torres, Federico, Herberg, Jethro A, de Jonge, Marien I, Levin, Michael, Kuijpers, Taco W, Kaforou, Myrsini, Jackson, Heather Ruth, Zandstra, Judith, Menikou, Stephanie, Hamilton, Shea, McArdle, Andrew J, De, Tisham, Agyeman, Philipp K A, Von Both, Ulrich, Carrol, Enitan D, Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, De Groot, Ronald, Moll, Henriette A, Pokorn, Marko, Pollard, Andrew, Schlapbach, Luregn J, Tsolia, Maria, Usuf, Effua, Wright, Victoria, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan JM, Cunnington, Aubrey J, Martinon-Torres, Federico, Herberg, Jethro, De Jonge, Marien I, Levin, Michael, Kuijpers, Taco, Kaforou, Myrsini, Abdulla, Amina, Aebi, Christoph, Agbeko, Rachel, Ali, Ladan, Alkema, Wynand, Allen, Karen, Anderson, Suzanne, Ansari, Imran, Arif, Tasnim, Avramoska, Tanja, Baas, Bryan, Bahovec, Natalija, Balode, Anda, Bãrdzdina, Arta, Barendregt, A M, Barral-Arca, Ruth, Bath, David, Bauchinger, Sebastian, Baumard, Lucas, Baumgart, Hinrich, Baxter, Frances, Bell, Kathryn, Bell, Ashley, Bello, Xabier, Bellos, Evangelos, Benesch, Martin, Bennet, Joshua, Berger, Christoph, Bernhard-Stirnemann, Sara, Bibi, Sagida, Bidlingmaier, Christoph, Binder, Alexander, Binder, Vera, Blackmore, Jennifer, Bojang, Kalifa, Borensztajn, Dorine M, Brengel-Pesce, Karen, Broderick, Claire, Buschbeck, Judith, Calvo-Bado, Leonides, Carnota, Sandra, Carter, Michael J, Castro, María Barreiro, Cebey-López, Miriam, Ceesay, Samba, Ceolotto, Astrid, Chan, Adora, Cocklin, Elizabeth, Collings, Kalvin, Crulley, Stephen, Curras-Tuala, María José, D'alessandro, Umberto, D'Souza, Giselle, Danhauser, Katharina, Darboe, Saffiatou, Darnell, Sarah, De Haan, L, De Vries, Gabriella, Deksne, Dãrta, Devine, Kirsty, Dewez, Juan Emmanuel, Dik, W, Dudley, Julia, Eber, Ernst, Fabian, Daniel, Farto, Cristina Balo, Fernández, Sonia Serén, Fidler, Katy, Fitchett, Elizabeth, Galassini, Rachel, Gallisti, Siegfried, García, Mirian Ben, Gardovska, Dace, Geissler, J, Gerrits, G P J M, Giannoni, Eric, Gloerich, Jolein, Gómez-Carballa, Alberto, González, Fernando Álves, Gores, Gunther, Grãvele, Dagne, Griese, Matthias, Grope, Ilze, Gurung, Meeru, Haas, Nikolaus, Habgood-Coote, Dominic, Hagedoorn, Nienke N, Haidl, Harald, Harrison, Rebekah, Hauer, Almuthe, Heidema, J, Heininger, Ulrich, Henriet, Stefanie, Hibberd, Martin, Hoggart, Cllive, Hösele, Susanne, Hourmat, Sara, Hude, Christa, Huijnen, Martijn, Iglesias, Pilar Leboráns, Iglesias, Marisol Vilas, Jennings, Rebecca, Johnson, Joanne, Jongerius, Ilse, Jorgensen, Rikke, Kahlert, Christian, Kandasamy, Rama, Kappler, Matthias, Keldorfer, Markus, Kelly, Dominic F, Khanijau, Aakash, Kim, Nayoung, Kim, Eunjung, King, Sharon, Kolberg, Laura, Kolnik, Mojca, Kloosterhuis, Lieke, Kohlfürst, Daniela S, Kohlmaier, Benno, Krenn, Larissa, Leigh, Simon, Leitner, Manuel, Leurent, Baptiste, Lim, Emma, Lin, Naomi, Liu, Ching-Chuan, Löffler, Sabine, Lurz, Eberhard, Mackerness, Christine, Maconochie, Ian, Mallet, Francois, Marmarinos, Antonis, Martin, Alex, Martin, Mike, Martinón Sánchez, José María, Martinón-Torres, Nazareth, McAlinden, Paul, McDonald, Sam, McDonell, Anne, Meiere, Anija, Meierford, Anne, Miedema, C J, Miners, Alec, Mistry, Ravi, Mommert, Marine, Morris, Sophie, Muench, Georg, Murdoch, David R, Mustafa, Sobia, Natalucci, Giancarlo, Neeleman, C, Newall, Karen, Nichols, Samuel, Niederer-Loher, Anita, Niedrist, Tobias, Nijman, Ruud, Nokalna, Ieve, Nordberg, Gudrun, O'Connor, Daniel, Obihara, C C, Oliver, Zoe, Oosthoek, Wilma, Ora, Miguel Sadiki, Osterman, Veronika, Pachot, Alexandre, Pajkrt, D, Pardo-Seco, Jacobo, Pavãre, Jana, Paz, Ivonne Pena, Paulus, Stéphane, Pérez, Belén Mosquera, Persand, Salina, Pfleger, Andreas, Pfurtscheller, Klaus, Philipsen, Ria, Pickering, Alisa, Pierce, Benjamin, Pilch, Heidemarie, Pischedda, Sara, Pölz, Lena, Posfay-Barbe, Klara M, Powell, Oliver, Prunk, Petra, Pučuka, Zanda, Rajic, Glorija, Rashid, Aqeela, Redondo-Collazo, Lorenzo, Reiter, Karl, Relly, Christa, Rhodes, Mathew, Rial, Jose Gómez, Richmond, Vivien, Riedel, Thomas, Rivero Calle, Irene, Roca, Anna, Rödl, Siegfried, Rodríguez, Lidia Piñeiro, Rodríguez-Tenreiro, Carmen, Romaine, Sam, Rowlands, Emily, Rudzate, Aleksandra, Sagmeister, Manfred, Saidykhan, Momodou, Sallas, Antonio, Sarr, Isatou, Schoen, Carola, Schonenberg, D, Schweintzger, Nina, Secka, Fatou, Selecka, Katrīna, Shah, Priyen, Shen, Ching-Fen, Shrestha, Shrijana, Skrabl-Baumgartner, Andrea, Soon, Joshua, Sperl, Matthias, Sprenkeler, Evelien, Spyridis, Nikos, Srovin, Tina Plankar, Stampfer, Laura, Stevens, Molly, Stocker, Martin, Strenger, Volker, Suárez, Carlos Durán, Svile, Dace, Syggelou, Kelly, Tal, Chantal, Tambouratzi, Maria, Tavliavini, Emma, Thakker, Clare, Thomson, Evelyn, Throson, Stephen, Till, Holger, Tramper-Stranders, G A, Trasorras, Cristina Serén, Trobisch, Andreas, Urbãne, Urzula Nora, Usman, Mariama, Valentine, Lucille, Van Aerde, Koen, Van den Berg, J M, Van den Broek, Bryan, Van der Giessen, Ilona, Van der Kuip, M, Van der Velden, Fabian, Van Furth, A M, Van Gool, Alain J, Van Leur, M, van Mierlo, G, Vázquez, Sara Ray, Vermont, Clementien, Vicente, Luisa García, Vincek, Katarina, Vito, Ortensia, Voice, Marie, Wallia, Diane, Walsh, Ben, Wang, Shih-Min, Wedderburn, Catherine, Willems, Esther, Wilson, Clare, Wood, Amanda, Woodsford, Phil, Wyss, Verena, Xagorari, Marietta, Zachariasse, Joany, Zaman, Syed M A, Zurl, Christoph, and Zwerenz, Manuela

Abstract

Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h.

Published
2023
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4. PLANNER: A Multi-Scale Deep Language Model for the Origins of Replication Site Prediction

Author

Wang, Cong, He, Zhijie, Jia, Runchang, Pan, Shirui, Coin, Lachlan JM, Song, Jiangning, and Li, Fuyi

Abstract

Origins of replication sites (ORIs) are crucial genomic regions where DNA replication initiation takes place, playing pivotal roles in fundamental biological processes like cell division, gene expression regulation, and DNA integrity. Accurate identification of ORIs is essential for comprehending cell replication, gene expression, and mutation-related diseases. However, experimental approaches for ORI identification are often expensive and time-consuming, leading to the growing popularity of computational methods. In this study, we present PLANNER (DeeP LeArNiNg prEdictor for ORI), a novel approach for species-specific and cell-specific prediction of eukaryotic ORIs. PLANNER uses the multi-scale k-tuple sequences as input and employs the DNABERT pre-training model with transfer learning and ensemble learning strategies to train accurate predictive models. Extensive empirical test results demonstrate that PLANNER achieved superior predictive performance compared to state-of-the-art approaches, including iOri-Euk, Stack-ORI, and ORI-Deep, within specific cell types and across different cell types. Furthermore, by incorporating an interpretable analysis mechanism, we provide insights into the learned patterns, facilitating the mapping from discovering important sequential determinants to comprehensively analysing their biological functions.

Published
2024
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5. Assembly of whole-chromosome pseudomolecules for polyploid plant genomes using outbred mapping populations

Author

Zhou, Chenxi, Olukolu, Bode, Gemenet, Dorcus C., Wu, Shan, Gruneberg, Wolfgang, Cao, Minh Duc, Fei, Zhangjun, Zeng, Zhao-Bang, George, Andrew W., Khan, Awais, Yencho, G. Craig, and Coin, Lachlan J. M.

Abstract

Despite advances in sequencing technologies, assembly of complex plant genomes remains elusive due to polyploidy and high repeat content. Here we report PolyGembler for grouping and ordering contigs into pseudomolecules by genetic linkage analysis. Our approach also provides an accurate method with which to detect and fix assembly errors. Using simulated data, we demonstrate that our approach is of high accuracy and outperforms three existing state-of-the-art genetic mapping tools. Particularly, our approach is more robust to the presence of missing genotype data and genotyping errors. We used our method to construct pseudomolecules for allotetraploid lawn grass utilizing PacBio long reads in combination with restriction site-associated DNA sequencing, and for diploid Ipomoea trifidaand autotetraploid potato utilizing contigs assembled from Illumina reads in combination with genotype data generated by single-nucleotide polymorphism arrays and genotyping by sequencing, respectively. We resolved 13 assembly errors for a published I. trifidagenome assembly and anchored eight unplaced scaffolds in the published potato genome.

Published
2020
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6. Sustained transmission over two decades of a previously unrecognised MPT64 negative Mycobacterium tuberculosisstrain in Queensland, Australia: a whole genome sequencing study

Author

Bainomugisa, Arnold, Pandey, Sushil, OConnor, Bridget, Syrmis, Melanie, Whiley, David, Sintchenko, Vitali, Coin, Lachlan, Marais, Ben J., and Coulter, Christopher

Abstract

MPT64 is a key protein used for Mycobacterium tuberculosis(MTB) complex strain identification. We describe protracted transmission of an MPT64 negative MTB strain in Queensland, Australia, and explore genomic factors related to its successful spread.

Published
2024
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7. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Author

Martinón-Torres, Federico, Salas, Antonio, Rivero-Calle, Irene, Cebey-López, Miriam, Pardo-Seco, Jacobo, Herberg, Jethro A, Boeddha, Navin P, Klobassa, Daniela S, Secka, Fatou, Paulus, Stephane, de Groot, Ronald, Schlapbach, Luregn J, Driessen, Gertjan J, Anderson, Suzanne T, Emonts, Marieke, Zenz, Werner, Carrol, Enitan D, Van der Flier, Michiel, Levin, Michael, Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Herberg, Jethro, Hourmat, Bernardo, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Bellos, Evangelos, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stefanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Thakker, Clare, Bokhandi, Sumit, Power, Sue, Barham, Heather, Pathan, Nazima, Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, Saul, Patel, Sanjay, McCorkell, Jenni, Davies, Patrick, Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, Raghu, Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C, White, Sonia, Fortune, Peter Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas Ellacuriaga, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Serén Fernández, Sonia, Porto Silva, María del Sol, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, León León, María Cruz, Navarro Mingorance, Álvaro, Gabaldó Barrios, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Ruiz Contreras, Jesús, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, Lozano, María José, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, María del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, Ronald, van Furth, A. Marceline, van der Flier, Michiel, Boeddha, Navin Prekash, Driessen, Gertjan JA, Emonts, Marieke, Hazelzet, Jan A, Kuijpers, Taco W, Pajkrt, Dasja, Sanders, Elisabeth AM, van de Beek, Diederik, van der Ende, Arie, Philipsen, Ria LA, Adeel, Abdul OA, Breukels, Meike A, Brinkman, Danielle MC, de Korte, Carla CMM, de Vries, Esther, de Waal, Wouter J, Dekkers, Roel, Dings-Lammertink, Anouk, Doedens, Rienus A, Donker, Albertine E, Dousma, Mieke, Faber, Tina E, Gerrits, G Peter JM, Gerver, Jan AM, Heidema, Jojanneke, Homan-van der Veen, Jenneke, Jacobs, Monique AM, Jansen, Nicolaas JG, Kawczynski, Pawel, Klucovska, Kristine, Kneyber, Martin CJ, Koopman-Keemink, Yvonne, Langenhorst, Veerle J, Leusink, José, Loza, Bettina F, Merth, Istvan T, Miedema, Carien J, Neeleman, Chris, Noordzij, Jeroen G, Obihara, Charles C, van Overbeek - van Gils, A Lidy T, Poortman, Geriska H, Potgieter, Steph T, Potjewijd, Joke, Rosias, Philippe PR, Sprong, Tom, ten Tussher, Gavin W, Thio, Boony J, Tramper-Stranders, Gerdien A, van Deuren, Marcel, van der Meer, Henny, van Kuppevelt, Andre JM, van Wermeskerken, Anne-Marie, Verwijs, Wim A, Wolfs, Tom FW, Schlapbach, Luregn Jan, Agyeman, Philipp, Aebi, Christoph, Berger, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M, Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan, Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel Sarah, Anderson, Suzanne T, Secka, Fatou, Bojang, Kalifa A, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Klobassa, Daniela Sabine, Binder, Alexander, Schweintzger, Nina Alexandra, Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, and Žukovskaja, Veslava

Abstract

Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe.

Published
2018
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8. Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

Author

Poznik, G David, Xue, Yali, Mendez, Fernando L, Willems, Thomas F, Massaia, Andrea, Wilson Sayres, Melissa A, Ayub, Qasim, McCarthy, Shane A, Narechania, Apurva, Kashin, Seva, Chen, Yuan, Banerjee, Ruby, Rodriguez-Flores, Juan L, Cerezo, Maria, Shao, Haojing, Gymrek, Melissa, Malhotra, Ankit, Louzada, Sandra, Desalle, Rob, Ritchie, Graham R S, Cerveira, Eliza, Fitzgerald, Tomas W, Garrison, Erik, Marcketta, Anthony, Mittelman, David, Romanovitch, Mallory, Zhang, Chengsheng, Zheng-Bradley, Xiangqun, Abecasis, Gonçalo R, McCarroll, Steven A, Flicek, Paul, Underhill, Peter A, Coin, Lachlan, Zerbino, Daniel R, Yang, Fengtang, Lee, Charles, Clarke, Laura, Auton, Adam, Erlich, Yaniv, Handsaker, Robert E, Bustamante, Carlos D, and Tyler-Smith, Chris

Abstract

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations.

Published
2016
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9. A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections

Author

Blaskovich, Mark A. T., Hansford, Karl A., Butler, Mark S., Ramu, Soumya, Kavanagh, Angela M., Jarrad, Angie M., Prasetyoputri, Anggia, Pitt, Miranda E., Huang, Johnny X., Lindahl, Fredrik, Ziora, Zyta M., Bradford, Tanya, Muldoon, Craig, Rajaratnam, Premraj, Pelingon, Ruby, Edwards, David J., Zhang, Bing, Amado, Maite, Elliott, Alysha G., Zuegg, Johannes, Coin, Lachlan, Woischnig, Anne-Kathrin, Khanna, Nina, Breidenstein, Elena, Stincone, Anna, Mason, Clive, Khan, Nawaz, Cho, Hye-Kyung, Karau, Melissa J., Greenwood-Quaintance, Kerryl E., Patel, Robin, Wootton, Mandy, James, Meagan L., Hutton, Melanie L., Lyras, Dena, Ogunniyi, Abiodun D., Mahdi, Layla K., Trott, Darren J., Wu, Xiaoqian, Niles, Samantha, Lewis, Kim, Smith, Jordan R., Barber, Katie E., Yim, Juwon, Rice, Seth Alan, Rybak, Michael J., Ishmael, Chad R., Hori, Kellyn R., Bernthal, Nicholas M., Francis, Kevin P., Roberts, Jason A., Paterson, David L., and Cooper, Matthew A.

Abstract

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureusand Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90≤ 0.06 μg/ml) against hundreds of isolates of methicillin-resistant S. aureus(MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficileinfection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.

Published
2022
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10. Gene-Targeted Analysis of Copy Number Variants Identifies 3 Novel Associations With Coronary Heart Disease Traits.

Author

Costelloe, Seáin J., Moustafa, Julia S. El-Sayed, Drenos, Fotios, Li Qiao, Whiting, Stephen, Thomas, Michael, Kivimaki, Mika, Kumari, Meena, Hingorani, Aroon D., Tzoulaki, Ioanna, Marjo-Riitta, Järvelin, Aimo, Ruokonen, Hartikainen, Anna-Liisa, Pouta, Anneli, Walters, Robin G., Blakemore, Alexandra I. E., Humphries, Steve E., Coin, Lachlan J. M., Talmud, Philippa J., and Palmen, Jutta

Subjects
CORONARY disease, CARDIOVASCULAR diseases risk factors, HIGH density lipoproteins, APOLIPOPROTEINS, GENETICS
Abstract

The article discusses the study that uses data for 2500 men from the Second Northwick Park Heart Study (NPHS-II) to investigate the role of copy number variants (CNVs) in coronary heart disease (CHD) traits, using cnvHap algorithm for CNV detection. The study found the potential of CNV detection algorithms such as cnvHAP to be used for the identification of novel CNVs, of which some have shown to have significant association and replication with coronary heart disease (CHD) risk phenotypes.

Published
2012
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11. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.

Author

Ramasamy, Adaikalavan, Curjuric, Ivan, Coin, Lachlan J., Kumar, Ashish, McArdle, Wendy L., Imboden, Medea, Leynaert, Benedicte, Kogevinas, Manolis, Schmid-Grendelmeier, Peter, Pekkanen, Juha, Wjst, Matthias, Bircher, Andreas J., Sovio, Ulla, Rochat, Thierry, Hartikainen, Anna-Liisa, Balding, David J., Jarvelin, Marjo-Riitta, Probst-Hensch, Nicole, Strachan, David P., and Jarvis, Deborah L.

Subjects
META-analysis, ALLERGIC rhinitis, BIRTH order, IMMUNOGLOBULIN E, GENETIC polymorphisms, MEMBRANE proteins, LUNG diseases
Abstract

Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. Objective: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Method: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Results: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P grass = 1.6 × 10−9; P AR = 8.0 × 10−3). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P grass = 9.4 × 10−9; P AR = 3.8 × 10−8). The third genome-wide significant variant was rs17513503 (Pgrass = 1.2 × 10−8; PAR = 7.4 × 10−7) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. Conclusions: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. [ABSTRACT FROM AUTHOR]

Published
2011
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12. Transforming Growth Factor-β Signaling Pathway in Patients With Kawasaki Disease.

Author

Shimizu, Chisato, Davila, Sonia, Hibberd, Martin L., Lin, Kevin O., Molkara, Delaram, Frazer, Jeffrey R., Sun, Shelley, Baker, Annette L., Newburger, Jane W., Rowley, Anne H., Shulman, Stanford T., Burgner, David, Breunis, Willemijn, Kuipers, Taco W., Wright, Victoria J., Levin, Michael, Eleftherohorinou, Hariklia, Coin, Lachlan, Popper, Stephen J., and Relman, David A.

Subjects
TRANSFORMING growth factors, MUCOCUTANEOUS lymph node syndrome, MEDICAL genetics, DNA microarrays, HUMAN genetic variation, THERAPEUTICS
Abstract

The article discusses a research study on the importance of transforming growth factor (TGF)-β in the susceptibility to Kawasaki Disease (KD). Genetic variation in 15 genes on the TGF-β pathway of 771 patients with KD were analyzed as well as the transcript abundance patterns through microarray and reverse transcriptase-polymerase chain reaction and measurement of plasma TGF-β protein levels. Findings suggest that genetic variation in the pathway of TGF-β can influence susceptibility to KD, therapy response and disease outcome.

Published
2011
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13. Gene-Targeted Analysis of Copy Number Variants Identifies 3 Novel Associations With Coronary Heart Disease Traits

Author

Costelloe, Seán J., Moustafa, Julia S. El-Sayed, Drenos, Fotios, Palmen, Jutta, Qiao, Li, Whiting, Stephen, Thomas, Michael, Kivimaki, Mika, Kumari, Meena, Hingorani, Aroon D., Tzoulaki, Ioanna, Marjo-Riitta, Järvelin, Aimo, Ruokonen, Hartikainen, Anna-Liisa, Pouta, Anneli, Walters, Robin G., Blakemore, Alexandra I.F., Humphries, Steve E., Coin, Lachlan J. M., and Talmud, Philippa J.

Abstract

Copy number variants (CNVs) are a major form of genomic variation, which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited.

Published
2012
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14. Transforming Growth Factor- Signaling Pathway in Patients With Kawasaki Disease

Author

Shimizu, Chisato, Jain, Sonia, Davila, Sonia, Hibberd, Martin L., Lin, Kevin O., Molkara, Delaram, Frazer, Jeffrey R., Sun, Shelly, Baker, Annette L., Newburger, Jane W., Rowley, Anne H., Shulman, Stanford T., Burgner, David, Breunis, Willemijn B., Kuijpers, Taco W., Wright, Victoria J., Levin, Michael, Eleftherohorinou, Hariklia, Coin, Lachlan, Popper, Stephen J., Relman, David A., Fury, Wen, Lin, Calvin, Mellis, Scott, Tremoulet, Adriana H., and Burns, Jane C.

Abstract

Transforming growth factor (TGF)- is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF- signaling might be important in KD susceptibility and disease outcome.

Published
2011
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15. Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection

Author

Chang, Jessie J.-Y., Rawlinson, Daniel, Pitt, Miranda E., Taiaroa, George, Gleeson, Josie, Zhou, Chenxi, Mordant, Francesca L., De Paoli-Iseppi, Ricardo, Caly, Leon, Purcell, Damian F.J., Stinear, Timothy P., Londrigan, Sarah L., Clark, Michael B., Williamson, Deborah A., Subbarao, Kanta, and Coin, Lachlan J.M.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses subgenomic RNA (sgRNA) to produce viral proteins for replication and immune evasion. We apply long-read RNA and cDNA sequencing to in vitrohuman and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA upregulates earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of open reading frame 1ab (ORF1ab) containing nsp1joins to ORF10, and the 3′ untranslated region (UTR) upregulates at 48 h post-infection in human cell lines. We identify double-junction sgRNA containing both TRS-dependent and -independent junctions. We find multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA and that sgRNA modifications are stable across transcript clusters, host cells, and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle.

Published
2021
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16. Bioinformatics: living on the edge

Author

Bellos, Evangelos, Coin, Lachlan, and Kaforou, Myrsini

Abstract

A report on the 11th European Conference on Computational Biology (ECCB), Basel, Switzerland, September 9-12, 2012.

Published
2012
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17. Genotype-free demultiplexing of pooled single-cell RNA-seq

Author

Xu, Jun, Falconer, Caitlin, Nguyen, Quan, Crawford, Joanna, McKinnon, Brett D., Mortlock, Sally, Senabouth, Anne, Andersen, Stacey, Chiu, Han Sheng, Jiang, Longda, Palpant, Nathan J., Yang, Jian, Mueller, Michael D., Hewitt, Alex W., Pébay, Alice, Montgomery, Grant W., Powell, Joseph E., and Coin, Lachlan J.M

Abstract

A variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We introduce scSplit which utilizes genetic differences inferred from scRNA-seq data alone to demultiplex pooled samples. scSplit also enables mapping clusters to original samples. Using simulated, merged, and pooled multi-individual datasets, we show that scSplit prediction is highly concordant with demuxlet predictions and is highly consistent with the known truth in cell-hashing dataset. scSplit is ideally suited to samples without external genotype information and is available at: https://github.com/jon-xu/scSplit

Published
2019
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18. Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature

Author

Wright, Victoria J., Herberg, Jethro A., Kaforou, Myrsini, Shimizu, Chisato, Eleftherohorinou, Hariklia, Shailes, Hannah, Barendregt, Anouk M., Menikou, Stephanie, Gormley, Stuart, Berk, Maurice, Hoang, Long Truong, Tremoulet, Adriana H., Kanegaye, John T., Coin, Lachlan J. M., Glodé, Mary P., Hibberd, Martin, Kuijpers, Taco W., Hoggart, Clive J., Burns, Jane C., and Levin, Michael

Abstract

IMPORTANCE: To date, there is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms. OBJECTIVE: To identify a whole-blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions. DESIGN, SETTING, AND PARTICIPANTS: The case-control study comprised a discovery group that included a training and test set and a validation group of children with KD or comparator febrile illness. The setting was pediatric centers in the United Kingdom, Spain, the Netherlands, and the United States. The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, and 242 bacterial or viral infections) and 55 healthy controls. The independent validation group comprised 102 patients with KD, including 72 in the first 7 days of illness, and 130 febrile controls. The study dates were March 1, 2009, to November 14, 2013, and data analysis took place from January 1, 2015, to December 31, 2017. MAIN OUTCOMES AND MEASURES: Whole-blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (parallel regularized regression model search). The ability of transcript signatures (implemented as disease risk scores) to discriminate KD cases from controls was assessed by area under the curve (AUC), sensitivity, and specificity at the optimal cut point according to the Youden index. RESULTS: Among 404 patients in the discovery set, there were 78 with KD (median age, 27 months; 55.1% male) and 326 febrile controls (median age, 37 months; 56.4% male). Among 202 patients in the validation set, there were 72 with KD (median age, 34 months; 62.5% male) and 130 febrile controls (median age, 17 months; 56.9% male). A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set, with AUC of 96.2% (95% CI, 92.5%-99.9%), sensitivity of 81.7% (95% CI, 60.0%-94.8%), and specificity of 92.1% (95% CI, 84.0%-97.0%). In the validation set, the signature distinguished KD from febrile controls, with AUC of 94.6% (95% CI, 91.3%-98.0%), sensitivity of 85.9% (95% CI, 76.8%-92.6%), and specificity of 89.1% (95% CI, 83.0%-93.7%). The signature was applied to clinically defined categories of definite, highly probable, and possible KD, resulting in AUCs of 98.1% (95% CI, 94.5%-100%), 96.3% (95% CI, 93.3%-99.4%), and 70.0% (95% CI, 53.4%-86.6%), respectively, mirroring certainty of clinical diagnosis. CONCLUSIONS AND RELEVANCE: In this study, a 13-transcript blood gene expression signature distinguished KD from other febrile conditions. Diagnostic accuracy increased with certainty of clinical diagnosis. A test incorporating the 13-transcript disease risk score may enable earlier diagnosis and treatment of KD and reduce inappropriate treatment in those with other diagnoses.

Published
2018
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20. cnvHiTSeq: integrative models for high-resolution copy number variation detection and genotyping using population sequencing data

Author

Bellos, Evangelos, Johnson, Michael, and M Coin, Lachlan

Abstract

Recent advances in sequencing technologies provide the means for identifying copy number variation (CNV) at an unprecedented resolution. A single next-generation sequencing experiment offers several features that can be used to detect CNV, yet current methods do not incorporate all available signatures into a unified model. cnvHiTSeq is an integrative probabilistic method for CNV discovery and genotyping that jointly analyzes multiple features at the population level. By combining evidence from complementary sources, cnvHiTSeq achieves high genotyping accuracy and a substantial improvement in CNV detection sensitivity over existing methods, while maintaining a low false discovery rate. cnvHiTSeq is available at http://sourceforge.net/projects/cnvhitseq

Published
2012
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21. Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms

Author

Barrenäs, Fredrik, Chavali, Sreenivas, Alves, Alexessander, Coin, Lachlan, Jarvelin, Marjo-Riitta, Jörnsten, Rebecka, Langston, Michael, Ramasamy, Adaikalavan, Rogers, Gary, Wang, Hui, and Benson, Mikael

Abstract

Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.

Published
2012
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22. Haplotype and isoform specific expression estimation using multi-mapping RNA-seq reads

Author

Turro, Ernest, Su, Shu-Yi, Gonçalves, Ângela, Coin, Lachlan, Richardson, Sylvia, and Lewin, Alex

Abstract

We present a novel pipeline and methodology for simultaneously estimating isoform expression and allelic imbalance in diploid organisms using RNA-seq data. We achieve this by modeling the expression of haplotype-specific isoforms. If unknown, the two parental isoform sequences can be individually reconstructed. A new statistical method, MMSEQ, deconvolves the mapping of reads to multiple transcripts (isoforms or haplotype-specific isoforms). Our software can take into account non-uniform read generation and works with paired-end reads.

Published
2011
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