Search

Your search keyword '"Gupta, Ramneek"' showing total 520 results
Start Over Author "Gupta, Ramneek"
520 results on '"Gupta, Ramneek"'

1. Large Language Model-informed ECG Dual Attention Network for Heart Failure Risk Prediction

Author

Chen, Chen, Li, Lei, Beetz, Marcel, Banerjee, Abhirup, Gupta, Ramneek, and Grau, Vicente

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Artificial Intelligence, Computer Science - Computation and Language, Computer Science - Machine Learning, Electrical Engineering and Systems Science - Signal Processing
Abstract

Heart failure (HF) poses a significant public health challenge, with a rising global mortality rate. Early detection and prevention of HF could significantly reduce its impact. We introduce a novel methodology for predicting HF risk using 12-lead electrocardiograms (ECGs). We present a novel, lightweight dual-attention ECG network designed to capture complex ECG features essential for early HF risk prediction, despite the notable imbalance between low and high-risk groups. This network incorporates a cross-lead attention module and twelve lead-specific temporal attention modules, focusing on cross-lead interactions and each lead's local dynamics. To further alleviate model overfitting, we leverage a large language model (LLM) with a public ECG-Report dataset for pretraining on an ECG-report alignment task. The network is then fine-tuned for HF risk prediction using two specific cohorts from the UK Biobank study, focusing on patients with hypertension (UKB-HYP) and those who have had a myocardial infarction (UKB-MI).The results reveal that LLM-informed pre-training substantially enhances HF risk prediction in these cohorts. The dual-attention design not only improves interpretability but also predictive accuracy, outperforming existing competitive methods with C-index scores of 0.6349 for UKB-HYP and 0.5805 for UKB-MI. This demonstrates our method's potential in advancing HF risk assessment with clinical complex ECG data., Comment: Under journal revision

Published
2024

4. RWOP1 Genetic risk factors associated with the multimorbid development of chronic kidney disease by cardiovascular disease patients

Author

Ennis, Matthew, primary, McClean, Paula, additional, Shukla, Priyank, additional, Sharman, Joanna L, additional, Leal, Luis G, additional, McVey, Zahra, additional, Nielsen, Rikke L, additional, Hu, Sile, additional, Fadista, Joao PS, additional, Das, Vivek, additional, Ramirez, Mar G, additional, Kitchen, Robert, additional, Gupta, Ramneek, additional, and Watterson, Steven, additional

Published
2024
Full Text
View/download PDF

7. Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia

Author

Tulstrup, Morten, Moriyama, Takaya, Jiang, Chuang, Grosjean, Marie, Nersting, Jacob, Abrahamsson, Jonas, Grell, Kathrine, Hjalgrim, Lisa Lyngsie, Jónsson, Ólafur Gísli, Kanerva, Jukka, Lund, Bendik, Nielsen, Stine Nygaard, Nielsen, Rikke Linnemann, Overgaard, Ulrik, Quist-Paulsen, Petter, Pruunsild, Kaie, Vaitkeviciene, Goda, Wolthers, Benjamin Ole, Zhang, Hui, Gupta, Ramneek, Yang, Jun J., and Schmiegelow, Kjeld

Published
2020
Full Text
View/download PDF

10. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children.

Author

Xu, Heng, Zhang, Hui, Yang, Wenjian, Yadav, Rachita, Morrison, Alanna C, Qian, Maoxiang, Devidas, Meenakshi, Liu, Yu, Perez-Andreu, Virginia, Zhao, Xujie, Gastier-Foster, Julie M, Lupo, Philip J, Neale, Geoff, Raetz, Elizabeth, Larsen, Eric, Bowman, W Paul, Carroll, William L, Winick, Naomi, Williams, Richard, Hansen, Torben, Holm, Jens-Christian, Mardis, Elaine, Fulton, Robert, Pui, Ching-Hon, Zhang, Jinghui, Mullighan, Charles G, Evans, William E, Hunger, Stephen P, Gupta, Ramneek, Schmiegelow, Kjeld, Loh, Mignon L, Relling, Mary V, and Yang, Jun J

Subjects
Hematopoietic Stem Cells, Animals, Humans, Mice, Genetic Predisposition to Disease, DNA-Binding Proteins, Transcription Factors, Case-Control Studies, Mutagenesis, Site-Directed, Genotype, Germ-Line Mutation, Mutation, Missense, Child, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p15, Ikaros Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genetic Variation, Genome-Wide Association Study, HEK293 Cells, Mutagenesis, Site-Directed, Mutation, Missense
Abstract

There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10(-23), odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16(INK4A), increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A-CDKN2B tumour suppressors in leukaemogenesis.

Published
2015

12. The genome of a Late Pleistocene human from a Clovis burial site in western Montana.

Author

Rasmussen, Morten, Anzick, Sarah, Waters, Michael, Skoglund, Pontus, DeGiorgio, Michael, Stafford, Thomas, Rasmussen, Simon, Moltke, Ida, Albrechtsen, Anders, Doyle, Shane, Poznik, G, Gudmundsdottir, Valborg, Yadav, Rachita, Malaspinas, Anna-Sapfo, White, Samuel, Allentoft, Morten, Tambets, Kristiina, Eriksson, Anders, Heintzman, Peter, Karmin, Monika, Korneliussen, Thorfinn, Meltzer, David, Pierre, Tracey, Stenderup, Jesper, Saag, Lauri, Warmuth, Vera, Lopes, Margarida, Malhi, Ripan, Brunak, Søren, Sicheritz-Ponten, Thomas, Barnes, Ian, Collins, Matthew, Orlando, Ludovic, Balloux, Francois, Manica, Andrea, Gupta, Ramneek, Metspalu, Mait, Bustamante, Carlos, Jakobsson, Mattias, Willerslev, Eske, Nielsen, Rasmus, and Cornejo, Omar

Subjects
Archaeology, Asia, Bone and Bones, Burial, Chromosomes, Human, Y, DNA, Mitochondrial, Emigration and Immigration, Europe, Gene Flow, Genome, Human, Haplotypes, History, Ancient, Humans, Indians, North American, Infant, Male, Models, Genetic, Molecular Sequence Data, Montana, Phylogeny, Population Dynamics, Radiometric Dating
Abstract

Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 (14)C years before present (bp) (13,000 to 12,600 calendar years bp). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology. However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans. An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum. Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 ± 35 (14)C years bp (approximately 12,707-12,556 calendar years bp) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4× and show that the gene flow from the Siberian Upper Palaeolithic Malta population into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years bp. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.

Published
2014

13. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium

Author

Koivula, Robert W., Forgie, Ian M., Kurbasic, Azra, Viñuela, Ana, Heggie, Alison, Giordano, Giuseppe N., Hansen, Tue H., Hudson, Michelle, Koopman, Anitra D. M., Rutters, Femke, Siloaho, Maritta, Allin, Kristine H., Brage, Søren, Brorsson, Caroline A., Dawed, Adem Y., De Masi, Federico, Groves, Christopher J., Kokkola, Tarja, Mahajan, Anubha, Perry, Mandy H., Rauh, Simone P., Ridderstråle, Martin, Teare, Harriet J. A., Thomas, E. Louise, Tura, Andrea, Vestergaard, Henrik, White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline W., Brunak, Søren, Dermitzakis, Emmanouil T., Froguel, Philippe, Frost, Gary, Gupta, Ramneek, Hansen, Torben, Hattersley, Andrew, Jablonka, Bernd, Kaye, Jane, Laakso, Markku, McDonald, Timothy J., Pedersen, Oluf, Schwenk, Jochen M., Pavo, Imre, Mari, Andrea, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Franks, Paul W., and for the IMI DIRECT Consortium

Published
2019
Full Text
View/download PDF

14. Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using an interpretable machine learning framework: a UK biobank study

Author

Gupta, Ramneek, primary, Nielsen, Rikke Linnemann, additional, Monfeuga, Thomas, additional, Kitchen, Robert, additional, Egerod, Line, additional, Leal, Luis, additional, Schreyer, August, additional, Sun, Carol, additional, Helenius, Marianne, additional, Simonsen, Lotte, additional, Willert, Marianne, additional, Tahrani, Abd, additional, and McVey, Zahra, additional

Published
2023
Full Text
View/download PDF

16. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstråle, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Viñuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark I., Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Published
2020
Full Text
View/download PDF

17. Data integration for prediction of weight loss in randomized controlled dietary trials

Author

Nielsen, Rikke Linnemann, Helenius, Marianne, Garcia, Sara L., Roager, Henrik M., Aytan-Aktug, Derya, Hansen, Lea Benedicte Skov, Lind, Mads Vendelbo, Vogt, Josef K., Dalgaard, Marlene Danner, Bahl, Martin I., Jensen, Cecilia Bang, Muktupavela, Rasa, Warinner, Christina, Aaskov, Vincent, Gøbel, Rikke, Kristensen, Mette, Frøkiær, Hanne, Sparholt, Morten H., Christensen, Anders F., Vestergaard, Henrik, Hansen, Torben, Kristiansen, Karsten, Brix, Susanne, Petersen, Thomas Nordahl, Lauritzen, Lotte, Licht, Tine Rask, Pedersen, Oluf, and Gupta, Ramneek

Published
2020
Full Text
View/download PDF

18. NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia

Author

Tulstrup, Morten, Grosjean, Marie, Nielsen, Stine Nygaard, Grell, Kathrine, Wolthers, Benjamin Ole, Wegener, Peder Skov, Jonsson, Olafur Gisli, Lund, Bendik, Harila-Saari, Arja, Abrahamsson, Jonas, Vaitkeviciene, Goda, Pruunsild, Kaie, Toft, Nina, Holm, Mette, Hulegårdh, Erik, Liestøl, Sigurd, Griskevicius, Laimonas, Punab, Mari, Wang, Jinhua, Carroll, William L., Zhang, Zeyu, Dalgaard, Marlene D., Gupta, Ramneek, Nersting, Jacob, and Schmiegelow, Kjeld

Published
2018
Full Text
View/download PDF

20. Predicting Hearing Loss in Testicular Cancer Patients after Cisplatin-Based Chemotherapy

Author

Garcia, Sara L., Lauritsen, Jakob, Christiansen, Bernadette K., Hansen, Ida F., Bandak, Mikkel, Dalgaard, Marlene D., Daugaard, Gedske, Gupta, Ramneek, Garcia, Sara L., Lauritsen, Jakob, Christiansen, Bernadette K., Hansen, Ida F., Bandak, Mikkel, Dalgaard, Marlene D., Daugaard, Gedske, and Gupta, Ramneek

Abstract

Testicular cancer is predominantly curable, but the long-term side effects of chemotherapy have a severe impact on life quality. In this research study, we focus on hearing loss as a part of overall chemotherapy-induced ototoxicity. This is a unique approach where we combine clinical data from the acclaimed nationwide Danish Testicular Cancer (DaTeCa)-Late database. Clinical and genetic data on 433 patients were collected from hospital files in October 2014. Hearing loss was classified according to the FACT/GOG-Ntx-11 version 4 self-reported Ntx6. Machine learning models combining a genome-wide association study within a nested cross-validated logistic regression were applied to identify patients at high risk of hearing loss. The model comprising clinical and genetic data identified 67% of the patients with hearing loss; however, this was with a false discovery rate of 49%. For the non-affected patients, the model identified 66% of the patients with a false omission rate of 19%. An area under the receiver operating characteristic (ROC-AUC) curve of 0.73 (95% CI, 0.71–0.74) was obtained, and the model suggests genes SOD2 and MGST3 as important in improving prediction over the clinical-only model with a ROC-AUC of 0.66 (95% CI, 0.65–0.66). Such prediction models may be used to allow earlier detection and prevention of hearing loss. We suggest a possible biological mechanism for cisplatin-induced hearing loss development. On confirmation in larger studies, such models can help balance treatment in clinical practice.

Published
2023

21. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Author

Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., Viñuela, Ana, Brown, Andrew A., Fernandez-Tajes, Juan J., Hong, Mun gwan, Brorsson, Caroline A., Koivula, Robert W., Davtian, David, Dupuis, Théo, Sartori, Ambra, Michalettou, Theodora Dafni, Forgie, Ian M., Adam, Jonathan, Allin, Kristine H., Caiazzo, Robert, Cederberg, Henna, De Masi, Federico, Elders, Petra J.M., Giordano, Giuseppe N., Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison J., Howald, Cédric, Jones, Angus G., Kokkola, Tarja, Laakso, Markku, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Mourby, Miranda, Musholt, Petra B., Nilsson, Birgitte, Pattou, Francois, Penet, Deborah, Raverdy, Violeta, Ridderstråle, Martin, Romano, Luciana, Rutters, Femke, Sharma, Sapna, Teare, Harriet, ‘t Hart, Leen, Tsirigos, Konstantinos D., Vangipurapu, Jagadish, Vestergaard, Henrik, Brunak, Søren, Franks, Paul W., Frost, Gary, Grallert, Harald, Jablonka, Bernd, McCarthy, Mark I., Pavo, Imre, Pedersen, Oluf, Ruetten, Hartmut, Walker, Mark, Adragni, Kofi, Allesøe, Rosa Lundbye L., Artati, Anna A., Arumugam, Manimozhiyan, Atabaki-Pasdar, Naeimeh, Baltauss, Tania, Banasik, Karina, Barnett, Anna L., Baum, Patrick, Bell, Jimmy D., Beulens, Joline W., Bianzano, Susanna B., Bizzotto, Roberto, Bonnefond, Amelie, Cabrelli, Louise, Dale, Matilda, Dawed, Adem Y., de Preville, Nathalie, Dekkers, Koen F., Deshmukh, Harshal A., Dings, Christiane, Donnelly, Louise, Dutta, Avirup, Ehrhardt, Beate, Engelbrechtsen, Line, Eriksen, Rebeca, Fan, Yong, Ferrer, Jorge, Fitipaldi, Hugo, Forman, Annemette, Fritsche, Andreas, Froguel, Philippe, Gassenhuber, Johann, Gough, Stephen, Graefe-Mody, Ulrike, Grempler, Rolf, Groeneveld, Lenka, Groop, Leif, Gudmundsdóttir, Valborg, Gupta, Ramneek, Hennige, Anita M.H., Hill, Anita V., Holl, Reinhard W., Hudson, Michelle, Jacobsen, Ulrik Plesner, Jennison, Christopher, Johansen, Joachim, Jonsson, Anna, Karaderi, Tugce, Kaye, Jane, Kennedy, Gwen, Klintenberg, Maria, Kuulasmaa, Teemu, Lehr, Thorsten, Loftus, Heather, Lundgaard, Agnete Troen T., Mazzoni, Gianluca, McRobert, Nicky, McVittie, Ian, Nice, Rachel, Nicolay, Claudia, Nijpels, Giel, Palmer, Colin N., Pedersen, Helle K., Perry, Mandy H., Pomares-Millan, Hugo, Prehn, Cornelia P., Ramisch, Anna, Rasmussen, Simon, Robertson, Neil, Rodriquez, Marianne, Sackett, Peter, Scherer, Nina, Shah, Nisha, Sihinevich, Iryna, Slieker, Roderick C., Sondertoft, Nadja B., Steckel-Hamann, Birgit, Thomas, Melissa K., Thomas, Cecilia Engel E., Thomas, Elizabeth Louise L., Thorand, Barbara, Thorne, Claire E., Tillner, Joachim, Tura, Andrea, Uhlen, Mathias, van Leeuwen, Nienke, van Oort, Sabine, Verkindt, Helene, Vogt, Josef, Wad Sackett, Peter W., Wesolowska-Andersen, Agata, Whitcher, Brandon, White, Margaret W., Adamski, Jerzy, Schwenk, Jochen M., Pearson, Ewan R., Dermitzakis, Emmanouil T., and Viñuela, Ana

Abstract

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

Published
2023

24. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

Author

Jensen, Niels F., Stenvang, Jan, Beck, Mette K., Hanáková, Barbora, Belling, Kirstine C., Do, Khoa N., Viuff, Birgitte, Nygård, Sune B., Gupta, Ramneek, Rasmussen, Mads H., Tarpgaard, Line S., Hansen, Tine P., Budinská, Eva, Pfeiffer, Per, Bosman, Fred, Tejpar, Sabine, Roth, Arnaud, Delorenzi, Mauro, Andersen, Claus L., Rømer, Maria U., Brünner, Nils, and Moreira, José M.A.

Published
2015
Full Text
View/download PDF

25. Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Author

Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., de Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, Brunak, S. ren, Froguel, Philippe, Thomas, Cecilia Engel, Haussler, Ragna, Beulens, Joline, Rutters, Femke, Nijpels, Giel, van Oort, Sabine, Groeneveld, Lenka, Elders, Petra, Giorgino, Toni, Rodriquez, Marianne, Nice, Rachel, Perry, Mandy, Bianzano, Susanna, Graefe-Mody, Ulrike, Hennige, Anita, Grempler, Rolf, Baum, Patrick, Stærfeldt, Hans-Henrik, Shah, Nisha, Teare, Harriet, Ehrhardt, Beate, Tillner, Joachim, Dings, Christiane, Lehr, Thorsten, Scherer, Nina, Sihinevich, Iryna, Cabrelli, Louise, Loftus, Heather, Bizzotto, Roberto, Tura, Andrea, Dekkers, Koen, van Leeuwen, Nienke, Groop, Leif, Slieker, Roderick, Ramisch, Anna, Jennison, Christopher, McVittie, Ian, Frau, Francesca, Steckel-Hamann, Birgit, Adragni, Kofi, Thomas, Melissa, Pasdar, Naeimeh Atabaki, Fitipaldi, Hugo, Kurbasic, Azra, Mutie, Pascal, Pomares-Millan, Hugo, Bonnefond, Amelie, Canouil, Mickael, Caiazzo, Robert, Verkindt, Helene, Holl, Reinhard, Kuulasmaa, Teemu, Deshmukh, Harshal, Cederberg, Henna, Laakso, Markku, Vangipurapu, Jagadish, Dale, Matilda, Thorand, Barbara, Nicolay, Claudia, Fritsche, Andreas, Hill, Anita, Hudson, Michelle, Thorne, Claire, Allin, Kristine, Arumugam, Manimozhiyan, Jonsson, Anna, Engelbrechtsen, Line, Forman, Annemette, Dutta, Avirup, Sondertoft, Nadja, Fan, Yong, Gough, Stephen, Robertson, Neil, McRobert, Nicky, Wesolowska-Andersen, Agata, Brown, Andrew, Davtian, David, Dawed, Adem, Donnelly, Louise, Palmer, Colin, White, Margaret, Ferrer, Jorge, Whitcher, Brandon, Artati, Anna, Prehn, Cornelia, Adam, Jonathan, Grallert, Harald, Gupta, Ramneek, Sackett, Peter Wad, Nilsson, Birgitte, Tsirigos, Konstantinos, Eriksen, Rebeca, Jablonka, Bernd, Uhlen, Mathias, Gassenhuber, Johann, Baltauss, Tania, de Preville, Nathalie, Klintenberg, Maria, Abdalla, Moustafa, Lundgaard, Agnete Troen [0000-0001-7447-6560], Hernández Medina, Ricardo [0000-0001-6373-2362], Johansen, Joachim [0000-0001-7052-1870], Niu, Lili [0000-0003-4571-4368], Biel, Jorge Hernansanz [0000-0002-3125-2951], Benros, Michael Eriksen [0000-0003-4939-9465], Pedersen, Anders Gorm [0000-0001-9650-8965], Jacobsen, Ulrik Plesner [0000-0001-9181-6854], Koivula, Robert [0000-0002-1646-4163], Vinuela, Ana [0000-0003-3771-8537], Haid, Mark [0000-0001-6118-1333], Hong, Mun-Gwan [0000-0001-8603-8293], Kennedy, Gwen [0000-0002-9856-3236], Thomas, E Louise [0000-0003-4235-4694], Frost, Gary [0000-0003-0529-6325], Hansen, Tue Haldor [0000-0001-5948-8993], Kaye, Jane [0000-0002-7311-4725], Hattersley, Andrew [0000-0001-5620-473X], Ridderstråle, Martin [0000-0002-3270-9167], Pedersen, Oluf [0000-0002-3321-3972], Hansen, Torben [0000-0001-8748-3831], Schwenk, Jochen M [0000-0001-8141-8449], Rasmussen, Simon [0000-0001-6323-9041], Brunak, Søren [0000-0003-0316-5866], Apollo - University of Cambridge Repository, Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, General practice, ACS - Heart failure & arrhythmias, APH - Aging & Later Life, Graduate School, and APH - Methodology

Subjects
Biomedical Engineering, Type 2 diabetes, Bioengineering, Applied Microbiology and Biotechnology, Deep Learning, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Type 2, Machine learning, Molecular Medicine, Humans, Data integration, IMI DIRECT Consortium, Systems biology, Algorithms, Biotechnology
Abstract

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

Published
2023
Full Text
View/download PDF

26. Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Author

Molnos, Sophie, Wahl, Simone, Haid, Mark, Eekhoff, E. Marelise W., Pool, René, Floegel, Anna, Deelen, Joris, Much, Daniela, Prehn, Cornelia, Breier, Michaela, Draisma, Harmen H., van Leeuwen, Nienke, Simonis-Bik, Annemarie M. C., Jonsson, Anna, Willemsen, Gonneke, Bernigau, Wolfgang, Wang-Sattler, Rui, Suhre, Karsten, Peters, Annette, Thorand, Barbara, Herder, Christian, Rathmann, Wolfgang, Roden, Michael, Gieger, Christian, Kramer, Mark H. H., van Heemst, Diana, Pedersen, Helle K., Gudmundsdottir, Valborg, Schulze, Matthias B., Pischon, Tobias, de Geus, Eco J. C., Boeing, Heiner, Boomsma, Dorret I., Ziegler, Anette G., Slagboom, P. Eline, Hummel, Sandra, Beekman, Marian, Grallert, Harald, Brunak, Søren, McCarthy, Mark I., Gupta, Ramneek, Pearson, Ewan R., Adamski, Jerzy, and ’t Hart, Leen M.

Published
2017
Full Text
View/download PDF

27. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

Author

Hansen, Lea B. S., Roager, Henrik M., Søndertoft, Nadja B., Gøbel, Rikke J., Kristensen, Mette, Vallès-Colomer, Mireia, Vieira-Silva, Sara, Ibrügger, Sabine, Lind, Mads V., Mærkedahl, Rasmus B., Bahl, Martin I., Madsen, Mia L., Havelund, Jesper, Falony, Gwen, Tetens, Inge, Nielsen, Trine, Allin, Kristine H., Frandsen, Henrik L., Hartmann, Bolette, Holst, Jens Juul, Sparholt, Morten H., Holck, Jesper, Blennow, Andreas, Moll, Janne Marie, Meyer, Anne S., Hoppe, Camilla, Poulsen, Jørgen H., Carvalho, Vera, Sagnelli, Domenico, Dalgaard, Marlene D., Christensen, Anders F., Lydolph, Magnus Christian, Ross, Alastair B., Villas-Bôas, Silas, Brix, Susanne, Sicheritz-Pontén, Thomas, Buschard, Karsten, Linneberg, Allan, Rumessen, Jüri J., Ekstrøm, Claus T., Ritz, Christian, Kristiansen, Karsten, Nielsen, H. Bjørn, Vestergaard, Henrik, Færgeman, Nils J., Raes, Jeroen, Frøkiær, Hanne, Hansen, Torben, Lauritzen, Lotte, Gupta, Ramneek, Licht, Tine Rask, and Pedersen, Oluf

Published
2018
Full Text
View/download PDF

29. Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype-genotype study

Author

Bioquímica y biología molecular, Biokimika eta biologia molekularra, Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Ólafur Gisli, Lund, Bendik, Harila Saari, Arja, Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, López López, Elixabet, Waanders, Esmé, Madsen, Hans O., Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, Nielsen, Rikke Linnemann, Bioquímica y biología molecular, Biokimika eta biologia molekularra, Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Ólafur Gisli, Lund, Bendik, Harila Saari, Arja, Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, López López, Elixabet, Waanders, Esmé, Madsen, Hans O., Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, and Nielsen, Rikke Linnemann

Abstract

[EN] Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45 years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (rho(BCP-ALL )= -.17, rho(T-ALL )= -.19; p < 3 x 10(-4)). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (rho = .43, p << 2 x 10(-6)). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.

Published
2022

30. Characteristics of white blood cell count in acute lymphoblastic leukemia : A COST LEGEND phenotype-genotype study

Author

Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Olafur Gisli, Lund, Bendik, Harila-Saari, Arja H., Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, Lopez-Lopez, Elixabet, Waanders, Esme, Madsen, Hans O., Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, Nielsen, Rikke Linnemann, Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Olafur Gisli, Lund, Bendik, Harila-Saari, Arja H., Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, Lopez-Lopez, Elixabet, Waanders, Esme, Madsen, Hans O., Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, and Nielsen, Rikke Linnemann

Abstract

Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45 years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (rho(BCP-ALL )= -.17, rho(T-ALL )= -.19; p < 3 x 10(-4)). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (rho = .43, p << 2 x 10(-6)). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.

Published
2022
Full Text
View/download PDF

31. Can Machine Learning Models Predict Asparaginase-associated Pancreatitis in Childhood Acute Lymphoblastic Leukemia

Author

Nielsen, Rikke L., Wolthers, Benjamin O., Helenius, Marianne, Albertsen, Birgitte K., Clemmensen, Line, Nielsen, Kasper, Kanerva, Jukka, Niinimäki, Riitta, Frandsen, Thomas L., Attarbaschi, Andishe, Barzilai, Shlomit, Colombini, Antonella, Escherich, Gabriele, Aytan-Aktug, Derya, Liu, Hsi Che, Möricke, Anja, Samarasinghe, Sujith, Van Der Sluis, Inge M., Stanulla, Martin, Tulstrup, Morten, Yadav, Rachita, Zapotocka, Ester, Schmiegelow, Kjeld, Gupta, Ramneek, Nielsen, Rikke L., Wolthers, Benjamin O., Helenius, Marianne, Albertsen, Birgitte K., Clemmensen, Line, Nielsen, Kasper, Kanerva, Jukka, Niinimäki, Riitta, Frandsen, Thomas L., Attarbaschi, Andishe, Barzilai, Shlomit, Colombini, Antonella, Escherich, Gabriele, Aytan-Aktug, Derya, Liu, Hsi Che, Möricke, Anja, Samarasinghe, Sujith, Van Der Sluis, Inge M., Stanulla, Martin, Tulstrup, Morten, Yadav, Rachita, Zapotocka, Ester, Schmiegelow, Kjeld, and Gupta, Ramneek

Abstract

Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk. We integrated information on age, sex, and SNPs based on Illumina Omni2.5exome-8 arrays of patients with childhood ALL (N=1564, 244 with AAP aged 1.0 to 17.9 y) from 10 international ALL consortia into machine learning models including regression, random forest, AdaBoost and artificial neural networks. A model with only age and sex had area under the receiver operating characteristic curve (ROC-AUC) of 0.62. Inclusion of 6 pancreatitis candidate gene SNPs or 4 validated pancreatitis SNPs boosted ROC-AUC somewhat (0.67) while 30 SNPs, identified through our AAP genome-wide association study cohort, boosted performance (0.80). Most predictive features included rs10273639 (PRSS1-PRSS2), rs10436957 (CTRC), rs13228878 (PRSS1/PRSS2), rs1505495 (GALNTL6), rs4655107 (EPHB2) and age (1 to 7 y). Second AAP following asparaginase re-exposure was predicted with ROC-AUC: 0.65. The machine learning models assist individual-level risk assessment of AAP for future prevention trials, and may legitimize asparaginase re-exposure when AAP risk is predicted to be low.

Published
2022

32. Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype-genotype study

Author

Genetica Sectie Genoomdiagnostiek, Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Ólafur Gisli, Lund, Bendik, Harila-Saari, Arja, Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, Lopez-Lopez, Elixabet, Waanders, Esmé, Madsen, Hans O, Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, Nielsen, Rikke Linnemann, Genetica Sectie Genoomdiagnostiek, Helenius, Marianne, Vaitkeviciene, Goda, Abrahamsson, Jonas, Jonsson, Ólafur Gisli, Lund, Bendik, Harila-Saari, Arja, Vettenranta, Kim, Mikkel, Sirje, Stanulla, Martin, Lopez-Lopez, Elixabet, Waanders, Esmé, Madsen, Hans O, Marquart, Hanne Vibeke, Modvig, Signe, Gupta, Ramneek, Schmiegelow, Kjeld, and Nielsen, Rikke Linnemann

Published
2022

33. Acquisition of docetaxel resistance in breast cancer cells reveals upregulation of ABCB1 expression as a key mediator of resistance accompanied by discrete upregulation of other specific genes and pathways

Author

Hansen, Stine Ninel, Westergaard, David, Thomsen, Mathilde Borg Houlberg, Vistesen, Mette, Do, Khoa Nguyen, Fogh, Louise, Belling, Kirstine C., Wang, Jun, Yang, Huanming, Gupta, Ramneek, Ditzel, Henrik J., Moreira, José, Brünner, Nils, Stenvang, Jan, and Schrohl, Anne-Sofie

Published
2015
Full Text
View/download PDF

34. An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

Author

Rasmussen, Morten, Guo, Xiaosen, Wang, Yong, Lohmueller, Kirk E., Rasmussen, Simon, Albrechtsen, Anders, Skotte, Line, Lindgreen, Stinus, Metspalu, Mait, Jombart, Thibaut, Kivisild, Toomas, Zhai, Weiwei, Eriksson, Anders, Manica, Andrea, Orlando, Ludovic, De La Vega, Francisco M., Tridico, Silvana, Metspalu, Ene, Nielsen, Kasper, Ávila-Arcos, María C., Moreno-Mayar, J. Víctor, Muller, Craig, Dortch, Joe, Gilbert, M. Thomas P., Lund, Ole, Wesolowska, Agata, Karmin, Monika, Weinert, Lucy A., Wang, Bo, Li, Jun, Tai, Shuaishuai, Xiao, Fei, Hanihara, Tsunehiko, van Driem, George, Jha, Aashish R., Ricaut, François-Xavier, de Knijff, Peter, Migliano, Andrea B, Romero, Irene Gallego, Kristiansen, Karsten, Lambert, David M., Brunak, Søren, Forster, Peter, Brinkmann, Bernd, Nehlich, Olaf, Bunce, Michael, Richards, Michael, Gupta, Ramneek, Bustamante, Carlos D., Krogh, Anders, Foley, Robert A., Lahr, Marta M., Balloux, Francois, Sicheritz-Pontén, Thomas, Villems, Richard, Nielsen, Rasmus, Wang, Jun, and Willerslev, Eske

Published
2011
Full Text
View/download PDF

35. Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype–genotype study

Author

Helenius, Marianne, primary, Vaitkeviciene, Goda, additional, Abrahamsson, Jonas, additional, Jonsson, Ólafur Gisli, additional, Lund, Bendik, additional, Harila‐Saari, Arja, additional, Vettenranta, Kim, additional, Mikkel, Sirje, additional, Stanulla, Martin, additional, Lopez‐Lopez, Elixabet, additional, Waanders, Esmé, additional, Madsen, Hans O., additional, Marquart, Hanne Vibeke, additional, Modvig, Signe, additional, Gupta, Ramneek, additional, Schmiegelow, Kjeld, additional, and Nielsen, Rikke Linnemann, additional

Published
2022
Full Text
View/download PDF

36. Large-Scale Functional Genomics Screen to Identify Modulators of Human β-Cell Insulin Secretion

Author

Szczerbinska, Iwona, primary, Tessitore, Annamaria, additional, Hansson, Lena Kristina, additional, Agrawal, Asmita, additional, Ragel Lopez, Alejandro, additional, Helenius, Marianne, additional, Malinowski, Andrzej R., additional, Gilboa, Barak, additional, Ruby, Maxwell A., additional, Gupta, Ramneek, additional, and Ämmälä, Carina, additional

Published
2022
Full Text
View/download PDF

38. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium

Author

Koivula, Robert W., Heggie, Alison, Barnett, Anna, Cederberg, Henna, Hansen, Tue H., Koopman, Anitra D., Ridderstråle, Martin, Rutters, Femke, Vestergaard, Henrik, Gupta, Ramneek, Herrgård, Sanna, Heymans, Martijn W., Perry, Mandy H., Rauh, Simone, Siloaho, Maritta, Teare, Harriet J. A., Thorand, Barbara, Bell, Jimmy, Brunak, Søren, Frost, Gary, Jablonka, Bernd, Mari, Andrea, McDonald, Tim J., Dekker, Jacqueline M., Hansen, Torben, Hattersley, Andrew, Laakso, Markku, Pedersen, Oluf, Koivisto, Veikko, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Franks, Paul W., and for the DIRECT Consortium

Published
2014
Full Text
View/download PDF

44. Can Machine Learning Models Predict Asparaginase-associated Pancreatitis in Childhood Acute Lymphoblastic Leukemia

Author

Nielsen, Rikke L., primary, Wolthers, Benjamin O., additional, Helenius, Marianne, additional, Albertsen, Birgitte K., additional, Clemmensen, Line, additional, Nielsen, Kasper, additional, Kanerva, Jukka, additional, Niinimäki, Riitta, additional, Frandsen, Thomas L., additional, Attarbaschi, Andishe, additional, Barzilai, Shlomit, additional, Colombini, Antonella, additional, Escherich, Gabriele, additional, Aytan-Aktug, Derya, additional, Liu, Hsi-Che, additional, Möricke, Anja, additional, Samarasinghe, Sujith, additional, van der Sluis, Inge M., additional, Stanulla, Martin, additional, Tulstrup, Morten, additional, Yadav, Rachita, additional, Zapotocka, Ester, additional, Schmiegelow, Kjeld, additional, and Gupta, Ramneek, additional

Published
2021
Full Text
View/download PDF

45. Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study

Author

Atabaki-Pasdar, Naeimeh, primary, Pomares-Millan, Hugo, additional, Koivula, Robert W, additional, Tura, Andrea, additional, Brown, Andrew, additional, Viñuela, Ana, additional, Agudelo, Leandro, additional, Coral, Daniel, additional, van Oort, Sabine, additional, Allin, Kristine, additional, Chabanova, Elizaveta, additional, Cederberg, Henna, additional, De Masi, Federico, additional, Elders, Petra, additional, Tajes, Juan Fernandez, additional, Forgie, Ian M, additional, Hansen, Tue H, additional, Heggie, Alison, additional, Jones, Angus, additional, Kokkola, Tarja, additional, Mahajan, Anubha, additional, McDonald, Timothy J, additional, McEvoy, Donna, additional, Tsirigos, Konstantinos, additional, Teare, Harriet, additional, Vangipurapu, Jagadish, additional, Vestergaard, Henrik, additional, Adamski, Jerzy, additional, Beulens, Joline WJ, additional, Brunak, Søren, additional, Dermitzakis, Emmanouil, additional, Hansen, Torben, additional, Hattersley, Andrew T, additional, Laakso, Markku, additional, Pedersen, Oluf, additional, Ridderstråle, Martin, additional, Ruetten, Hartmut, additional, Rutters, Femke, additional, Schwenk, Jochen M, additional, Walker, Mark, additional, Giordano, Giuseppe N, additional, Ohlsson, Mattias, additional, Gupta, Ramneek, additional, Mari, Andrea, additional, McCarthy, Mark I, additional, Thomas, E Louise, additional, Bell, Jimmy D, additional, Pavo, Imre, additional, Pearson, Ewan R, additional, and Franks, Paul W, additional

Published
2021
Full Text
View/download PDF

47. Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

Author

Besenbacher, Søren, Liu, Siyang, Izarzugaza, José M. G., Grove, Jakob, Belling, Kirstine, Bork-Jensen, Jette, Huang, Shujia, Als, Thomas D., Li, Shengting, Yadav, Rachita, Rubio-García, Arcadio, Lescai, Francesco, Demontis, Ditte, Rao, Junhua, Ye, Weijian, Mailund, Thomas, Friborg, Rune M., Pedersen, Christian N. S., Xu, Ruiqi, Sun, Jihua, Liu, Hao, Wang, Ou, Cheng, Xiaofang, Flores, David, Rydza, Emil, Rapacki, Kristoffer, Damm Sørensen, John, Chmura, Piotr, Westergaard, David, Dworzynski, Piotr, Sørensen, Thorkild I. A., Lund, Ole, Hansen, Torben, Xu, Xun, Li, Ning, Bolund, Lars, Pedersen, Oluf, Eiberg, Hans, Krogh, Anders, Børglum, Anders D., Brunak, Søren, Kristiansen, Karsten, Schierup, Mikkel H., Wang, Jun, Gupta, Ramneek, Villesen, Palle, and Rasmussen, Simon

Published
2015
Full Text
View/download PDF

48. Identification of 22 novel loci associated with susceptibility to testicular germ cell tumors

Author

Pluta, John B., Pyle, Louise C., Bishop, D. Timothy, Benitez, Javier, Cortessis, Victoria K., Ferlin, Alberto, Gietema, Jourik A., Greene, Mark H., Grotmol, Tom, Gupta, Ramneek, Hamilton, Robert M, Hildebrandt, Michelle, Kiemeney, Lambertus A, Lessel, Davor, Rafnar, Thorunn, Richiardi, Lorenzo, Skotheim, Rolf I., Turnbull, Clare, Wiklund, Fredrik, Zheng, Tongzhang, Rajpert-De Meyts, Ewa, Schwartz, Stephen M., McGlynn, Katherine A., Kanetsky, Peter A, Nathanson, Katherine L., Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Abstract

Background: Testicular germ cell tumors (TGCT) are the most common cancers in young men of European ancestry aged 20 to 39 years. The incidence of TGCT has doubled over the past 20 years, yet no robust environmental risk factors for disease have been identified. Although TGCTs are treatable by surgery, radiation, and platinum-based chemotherapy, multiple long-term toxicities of treatment often occur impacting morbidity and mortality. Due to their high heritability and homogenous cell of origin, TGCTs are well suited to genome-wide association methods. The Testicular Cancer Consortium (TECAC) has brought together the largest genome-wise association study (GWAS) study of TGCT to date. Methods: We conducted a GWAS of 5,602 cases and 5,006 controls aggregated from 12 locations in the US and Europe. Logistic regression models adjusted for study center and genomic ancestry. Genotypes were imputed against the Human Haplotype Reference Consortium. Meta-analysis was performed to combine GWAS results with summary statistics from five previously published TGCT studies, UK Biobank, deCODE Genetics, and an independent set of cases and controls, for a total of 10,156 cases and 179,683 controls. Biologic function of loci was explored using PAINTOR annotated with ATAC-seq data of four TGCT cell lines, SPATIAL-seq data of the NTERA2 TGCT cell-line, and publicly available data from ENCODE. Polygenic risk scores (PRS) were computed using subject-level data from the 5,602 cases and 5,006 controls, and effect sizes of the novel hits derived from the meta-analysis. Results: 22 novel and 45 previously reported loci associated with TGCT surpassed genome-wide significance (p < 5e-08). We discovered additional markers in known susceptibility loci and identified novel regions associated with germ cell development and sex determination (e.g., BCL11, AR), immune function (e.g., TNXB, ITIH5), and for the first time identified genes associated with kinetochore activity (e.g., PPP2R5A, ANAPC2). All identified risk SNPs to date account for 42.3% of heritability. Men in the highest 1% of PRS had over a 15-fold increased risk of TGCT compared to those at the median PRS, and PRS overall had an AUC of 74.29%. Conclusions: Results from our TGCT meta-analysis continue to provide insights into biological pathways affecting germ cell specification, expression, and epigenetic reprogramming, and sex determination. Our results also uniquely place TGCT as the only cancer type in which inherited variants implicating kinetochore activity, critical for chromosomal segregation, have been identified. Citation Format: John Pluta, Louisa Pyle, Timothy Bishop, Javier Benitez, Victoria Cortessis, Alberto Ferlin, Jourik Gietema, Mark Greene, Thomas Grotmol, Ramneek Gupta, Robert Hamilton, Michelle Hildebrandt, Lambertus Kiemeney, Davor Lessel, Thorunn Rafnar, Lorenzo Richiardi, Rolf Skotheim, Clare Turnbull, Fredrik Wiklund, Tongzhang Zheng, Ewa Rajpert- De Meyts, Stephen Schwartz, Katherine McGlynn, Peter Kanetsky, Katherine Nathanson. Identification of 22 novel loci associated with susceptibility to testicular germ cell tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1203.

Published
2020

49. Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Author

Maretty, Lasse, Jensen, Jacob Malte, Petersen, Bent, Sibbesen, Jonas Andreas, Liu, Siyang, Villesen, Palle, Skov, Laurits, Belling, Kirstine, Theil Have, Christian, Izarzugaza, Jose M. G., Grosjean, Marie, Bork-Jensen, Jette, Grove, Jakob, Als, Thomas D., Huang, Shujia, Chang, Yuqi, Xu, Ruiqi, Ye, Weijian, Rao, Junhua, Guo, Xiaosen, Sun, Jihua, Cao, Hongzhi, Ye, Chen, van Beusekom, Johan, Espeseth, Thomas, Flindt, Esben, Friborg, Rune M., Halager, Anders E., Le Hellard, Stephanie, Hultman, Christina M., Lescai, Francesco, Li, Shengting, Lund, Ole, Lngren, Peter, Mailund, Thomas, Matey-Hernandez, Maria Luisa, Mors, Ole, Pedersen, Christian N. S., Sicheritz-Pontn, Thomas, Sullivan, Patrick, Syed, Ali, Westergaard, David, Yadav, Rachita, Li, Ning, Xu, Xun, Hansen, Torben, Krogh, Anders, Bolund, Lars, Srensen, Thorkild I. A., Pedersen, Oluf, Gupta, Ramneek, Rasmussen, Simon, Besenbacher, Sren, Brglum, Anders D., Wang, Jun, Eiberg, Hans, Kristiansen, Karsten, Brunak, Sren, and Schierup, Mikkel Heide

Subjects
DNA sequencing -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Lasse Maretty [1]; Jacob Malte Jensen [2, 3]; Bent Petersen [4]; Jonas Andreas Sibbesen [1]; Siyang Liu [1, 5]; Palle Villesen [2, 3, 6]; Laurits Skov [2, 3]; Kirstine [...]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results