Search

Your search keyword '"Törönen, Petri"' showing total 32 results
Start Over Author "Törönen, Petri" Publication Year Range Last 10 years
32 results on '"Törönen, Petri"'

1. The giant diploid faba genome unlocks variation in a global protein crop

Author

Jayakodi, Murukarthick, Golicz, Agnieszka A., Kreplak, Jonathan, Fechete, Lavinia I., Angra, Deepti, Bednář, Petr, Bornhofen, Elesandro, Zhang, Hailin, Boussageon, Raphaël, Kaur, Sukhjiwan, Cheung, Kwok, Čížková, Jana, Gundlach, Heidrun, Hallab, Asis, Imbert, Baptiste, Keeble-Gagnère, Gabriel, Koblížková, Andrea, Kobrlová, Lucie, Krejčí, Petra, Mouritzen, Troels W., Neumann, Pavel, Nadzieja, Marcin, Nielsen, Linda Kærgaard, Novák, Petr, Orabi, Jihad, Padmarasu, Sudharsan, Robertson-Shersby-Harvie, Tom, Robledillo, Laura Ávila, Schiemann, Andrea, Tanskanen, Jaakko, Törönen, Petri, Warsame, Ahmed O., Wittenberg, Alexander H. J., Himmelbach, Axel, Aubert, Grégoire, Courty, Pierre-Emmanuel, Doležel, Jaroslav, Holm, Liisa U., Janss, Luc L., Khazaei, Hamid, Macas, Jiří, Mascher, Martin, Smýkal, Petr, Snowdon, Rod J., Stein, Nils, Stoddard, Frederick L., Stougaard, Jens, Tayeh, Nadim, Torres, Ana M., Usadel, Björn, Schubert, Ingo, O’Sullivan, Donal Martin, Schulman, Alan H., and Andersen, Stig Uggerhøj

Published
2023
Full Text
View/download PDF

2. The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author

Zhou, Naihui, Jiang, Yuxiang, Bergquist, Timothy R, Lee, Alexandra J, Kacsoh, Balint Z, Crocker, Alex W, Lewis, Kimberley A, Georghiou, George, Nguyen, Huy N, Hamid, Md Nafiz, Davis, Larry, Dogan, Tunca, Atalay, Volkan, Rifaioglu, Ahmet S, Dalkıran, Alperen, Cetin Atalay, Rengul, Zhang, Chengxin, Hurto, Rebecca L, Freddolino, Peter L, Zhang, Yang, Bhat, Prajwal, Supek, Fran, Fernández, José M, Gemovic, Branislava, Perovic, Vladimir R, Davidović, Radoslav S, Sumonja, Neven, Veljkovic, Nevena, Asgari, Ehsaneddin, Mofrad, Mohammad RK, Profiti, Giuseppe, Savojardo, Castrense, Martelli, Pier Luigi, Casadio, Rita, Boecker, Florian, Schoof, Heiko, Kahanda, Indika, Thurlby, Natalie, McHardy, Alice C, Renaux, Alexandre, Saidi, Rabie, Gough, Julian, Freitas, Alex A, Antczak, Magdalena, Fabris, Fabio, Wass, Mark N, Hou, Jie, Cheng, Jianlin, Wang, Zheng, Romero, Alfonso E, Paccanaro, Alberto, Yang, Haixuan, Goldberg, Tatyana, Zhao, Chenguang, Holm, Liisa, Törönen, Petri, Medlar, Alan J, Zosa, Elaine, Borukhov, Itamar, Novikov, Ilya, Wilkins, Angela, Lichtarge, Olivier, Chi, Po-Han, Tseng, Wei-Cheng, Linial, Michal, Rose, Peter W, Dessimoz, Christophe, Vidulin, Vedrana, Dzeroski, Saso, Sillitoe, Ian, Das, Sayoni, Lees, Jonathan Gill, Jones, David T, Wan, Cen, Cozzetto, Domenico, Fa, Rui, Torres, Mateo, Warwick Vesztrocy, Alex, Rodriguez, Jose Manuel, Tress, Michael L, Frasca, Marco, Notaro, Marco, Grossi, Giuliano, Petrini, Alessandro, Re, Matteo, Valentini, Giorgio, Mesiti, Marco, Roche, Daniel B, Reeb, Jonas, Ritchie, David W, Aridhi, Sabeur, Alborzi, Seyed Ziaeddin, Devignes, Marie-Dominique, Koo, Da Chen Emily, Bonneau, Richard, Gligorijević, Vladimir, Barot, Meet, Fang, Hai, Toppo, Stefano, and Lavezzo, Enrico

Subjects
Human Genome, Networking and Information Technology R&D (NITRD), Genetics, Generic health relevance, Animals, Biofilms, Candida albicans, Drosophila melanogaster, Genome, Bacterial, Genome, Fungal, Humans, Locomotion, Memory, Long-Term, Molecular Sequence Annotation, Pseudomonas aeruginosa, Protein function prediction, Long-term memory, Biofilm, Critical assessment, Community challenge, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Published
2019

3. An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Author

Jiang, Yuxiang, Oron, Tal Ronnen, Clark, Wyatt T, Bankapur, Asma R, D’Andrea, Daniel, Lepore, Rosalba, Funk, Christopher S, Kahanda, Indika, Verspoor, Karin M, Ben-Hur, Asa, Koo, Da Chen Emily, Penfold-Brown, Duncan, Shasha, Dennis, Youngs, Noah, Bonneau, Richard, Lin, Alexandra, Sahraeian, Sayed ME, Martelli, Pier Luigi, Profiti, Giuseppe, Casadio, Rita, Cao, Renzhi, Zhong, Zhaolong, Cheng, Jianlin, Altenhoff, Adrian, Skunca, Nives, Dessimoz, Christophe, Dogan, Tunca, Hakala, Kai, Kaewphan, Suwisa, Mehryary, Farrokh, Salakoski, Tapio, Ginter, Filip, Fang, Hai, Smithers, Ben, Oates, Matt, Gough, Julian, Törönen, Petri, Koskinen, Patrik, Holm, Liisa, Chen, Ching-Tai, Hsu, Wen-Lian, Bryson, Kevin, Cozzetto, Domenico, Minneci, Federico, Jones, David T, Chapman, Samuel, BKC, Dukka, Khan, Ishita K, Kihara, Daisuke, Ofer, Dan, Rappoport, Nadav, Stern, Amos, Cibrian-Uhalte, Elena, Denny, Paul, Foulger, Rebecca E, Hieta, Reija, Legge, Duncan, Lovering, Ruth C, Magrane, Michele, Melidoni, Anna N, Mutowo-Meullenet, Prudence, Pichler, Klemens, Shypitsyna, Aleksandra, Li, Biao, Zakeri, Pooya, ElShal, Sarah, Tranchevent, Léon-Charles, Das, Sayoni, Dawson, Natalie L, Lee, David, Lees, Jonathan G, Sillitoe, Ian, Bhat, Prajwal, Nepusz, Tamás, Romero, Alfonso E, Sasidharan, Rajkumar, Yang, Haixuan, Paccanaro, Alberto, Gillis, Jesse, Sedeño-Cortés, Adriana E, Pavlidis, Paul, Feng, Shou, Cejuela, Juan M, Goldberg, Tatyana, Hamp, Tobias, Richter, Lothar, Salamov, Asaf, Gabaldon, Toni, Marcet-Houben, Marina, Supek, Fran, Gong, Qingtian, Ning, Wei, Zhou, Yuanpeng, Tian, Weidong, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Toppo, Stefano, Ferrari, Carlo, and Giollo, Manuel

Subjects
Genetics, Networking and Information Technology R&D (NITRD), Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Algorithms, Computational Biology, Databases, Protein, Gene Ontology, Humans, Molecular Sequence Annotation, Proteins, Software, Structure-Activity Relationship, Protein function prediction, Disease gene prioritization, q-bio.QM, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundA major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.ResultsWe conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.ConclusionsThe top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.

Published
2016

4. Global analysis of aging-related protein structural changes uncovers enzyme-polymerization-based control of longevity

Author

Paukštytė, Jurgita, primary, López Cabezas, Rosa María, additional, Feng, Yuehan, additional, Tong, Kai, additional, Schnyder, Daniela, additional, Elomaa, Ellinoora, additional, Gregorova, Pavlina, additional, Doudin, Matteo, additional, Särkkä, Meeri, additional, Sarameri, Jesse, additional, Lippi, Alice, additional, Vihinen, Helena, additional, Juutila, Juhana, additional, Nieminen, Anni, additional, Törönen, Petri, additional, Holm, Liisa, additional, Jokitalo, Eija, additional, Krisko, Anita, additional, Huiskonen, Juha, additional, Sarin, L. Peter, additional, Hietakangas, Ville, additional, Picotti, Paola, additional, Barral, Yves, additional, and Saarikangas, Juha, additional

Published
2023
Full Text
View/download PDF

5. Novel split quality measures for stratified multilabel cross validation with application to large and sparse gene ontology datasets

Author

Tiittanen, Henri, Holm, Liisa, Törönen, Petri, Organismal and Evolutionary Biology Research Programme, Institute of Biotechnology, Genetics, Bioinformatics, and Computational genomics

Subjects
Genomics (q-bio.GN), FOS: Computer and information sciences, Computer Science - Machine Learning, FOS: Biological sciences, Quantitative Biology - Genomics, 113 Computer and information sciences, Machine Learning (cs.LG)
Abstract

Multilabel learning is an important topic in machine learning research. Evaluating models in multilabel settings requires specific cross validation methods designed for multilabel data. In this article, we show that the most widely used cross validation split quality measures do not behave adequately with multilabel data that has strong class imbalance. We present improved measures and an algorithm, optisplit, for optimising cross validations splits. We present an extensive comparison of various types of cross validation methods in which we show that optisplit produces more even cross validation splits than the existing methods and that it is fast enough to be used on big Gene Ontology (GO) datasets., 15 pages, 2 figures

Published
2022
Full Text
View/download PDF

7. The giant diploid faba genome unlocks variation in a global protein crop

Author

Jayakodi, Murukarthick, primary, Golicz, Agnieszka A., additional, Kreplak, Jonathan, additional, Fechete, Lavinia I., additional, Angra, Deepti, additional, Bednář, Petr, additional, Bornhofen, Elesandro, additional, Zhang, Hailin, additional, Boussageon, Raphaël, additional, Kaur, Sukhjiwan, additional, Cheung, Kwok, additional, Čížková, Jana, additional, Gundlach, Heidrun, additional, Hallab, Asis, additional, Imbert, Baptiste, additional, Keeble-Gagnère, Gabriel, additional, Koblížková, Andrea, additional, Kobrlová, Lucie, additional, Krejčí, Petra, additional, Mouritzen, Troels W., additional, Neumann, Pavel, additional, Nadzieja, Marcin, additional, Nielsen, Linda Kærgaard, additional, Novák, Petr, additional, Orabi, Jihad, additional, Padmarasu, Sudharsan, additional, Robertson-Shersby-Harvie, Tom, additional, Robledillo, Laura Ávila, additional, Schiemann, Andrea, additional, Tanskanen, Jaakko, additional, Törönen, Petri, additional, Warsame, Ahmed O., additional, Wittenberg, Alexander H.J., additional, Himmelbach, Axel, additional, Aubert, Grégoire, additional, Courty, Pierre-Emmanuel, additional, Doležel, Jaroslav, additional, Holm, Liisa U., additional, Janss, Luc L., additional, Khazaei, Hamid, additional, Macas, Jiří, additional, Mascher, Martin, additional, Smýkal, Petr, additional, Snowdon, Rod J., additional, Stein, Nils, additional, Stoddard, Frederick L., additional, Tayeh, Nadim, additional, Torres, Ana M., additional, Usadel, Björn, additional, Schubert, Ingo, additional, O’Sullivan, Donal Martin, additional, Schulman, Alan H., additional, and Andersen, Stig Uggerhøj, additional

Published
2022
Full Text
View/download PDF

10. DALI shines a light on remote homologs: One hundred discoveries.

Author

Holm, Liisa, Laiho, Aleksi, Törönen, Petri, and Salgado, Marco

Abstract

Structural comparison reveals remote homology that often fails to be detected by sequence comparison. The DALI web server (http://ekhidna2.biocenter.helsinki.fi/dali) is a platform for structural analysis that provides database searches and interactive visualization, including structural alignments annotated with secondary structure, protein families and sequence logos, and 3D structure superimposition supported by color‐coded sequence and structure conservation. Here, we are using DALI to mine the AlphaFold Database version 1, which increased the structural coverage of protein families by 20%. We found 100 remote homologous relationships hitherto unreported in the current reference database for protein domains, Pfam 35.0. In particular, we linked 35 domains of unknown function (DUFs) to the previously characterized families, generating a functional hypothesis that can be explored downstream in structural biology studies. Other findings include gene fusions, tandem duplications, and adjustments to domain boundaries. The evidence for homology can be browsed interactively through live examples on DALI's website. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

12. Novel split quality measures for stratified multilabel Cross Validation with application to large and sparse gene ontology datasets

Author

Tiittanen, Henri, Holm, Liisa, Törönen, Petri, Tiittanen, Henri, Holm, Liisa, and Törönen, Petri

Abstract

Multilabel learning is an important topic in machine learning research. Evaluating models in multilabel settings requires specific cross validation methods designed for multilabel data. In this article, we show that the most widely used cross validation split quality measures do not behave adequately with multilabel data that has strong class imbalance. We present improved measures and an algorithm, optisplit, for optimising cross validations splits. We present an extensive comparison of various types of cross validation methods in which we show that optisplit produces more even cross validation splits than the existing methods and that it is fast enough to be used on big Gene Ontology (GO) datasets., Comment: 15 pages, 2 figures

Published
2021
Full Text
View/download PDF

13. Molecular Fingerprint and Developmental Regulation of the Tegmental GABAergic and Glutamatergic Neurons Derived from the Anterior Hindbrain

Author

Morello, Francesca, primary, Borshagovski, Daniel, additional, Survila, Mantas, additional, Tikker, Laura, additional, Sadik-Ogli, Samir, additional, Kirjavainen, Anna, additional, Estartús, Nuri, additional, Knaapi, Laura, additional, Lahti, Laura, additional, Törönen, Petri, additional, Mazutis, Linas, additional, Delogu, Alessio, additional, Salminen, Marjo, additional, Achim, Kaia, additional, and Partanen, Juha, additional

Published
2020
Full Text
View/download PDF

14. Epigenome-450K-wide methylation signatures of active cigarette smoking: The Young Finns Study

Author

Mishra, Pashupati P., primary, Hänninen, Ismo, additional, Raitoharju, Emma, additional, Marttila, Saara, additional, Mishra, Binisha H., additional, Mononen, Nina, additional, Kähönen, Mika, additional, Hurme, Mikko, additional, Raitakari, Olli, additional, Törönen, Petri, additional, Holm, Liisa, additional, and Lehtimäki, Terho, additional

Published
2020
Full Text
View/download PDF

15. Epigenome-450K-wide methylation signatures of active cigarette smoking : The Young Finns Study

Author

Mishra, Pashupati P., Hänninen, Ismo, Raitoharju, Emma, Marttila, Saara, Mishra, Binisha H., Mononen, Nina, Kähönen, Mika, Hurme, Mikko, Raitakari, Olli, Törönen, Petri, Holm, Liisa, Lehtimaki, Terho, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Tampere University, Institute of Biotechnology, Computational genomics, Genetics, Bioinformatics, and Organismal and Evolutionary Biology Research Programme

Subjects
Biolääketieteet - Biomedicine, CARDIOVASCULAR RISK, GLIOMA, 1182 Biochemistry, cell and molecular biology, DNA METHYLATION, ISLANDS, METAANALYSIS
Abstract

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium Hu-manMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR)

Published
2020

16. PANNZER—A practical tool for protein function prediction.

Author

Törönen, Petri and Holm, Liisa

Abstract

The facility of next‐generation sequencing has led to an explosion of gene catalogs for novel genomes, transcriptomes and metagenomes, which are functionally uncharacterized. Computational inference has emerged as a necessary substitute for first‐hand experimental evidence. PANNZER (Protein ANNotation with Z‐scoRE) is a high‐throughput functional annotation web server that stands out among similar publically accessible web servers in supporting submission of up to 100,000 protein sequences at once and providing both Gene Ontology (GO) annotations and free text description predictions. Here, we demonstrate the use of PANNZER and discuss future plans and challenges. We present two case studies to illustrate problems related to data quality and method evaluation. Some commonly used evaluation metrics and evaluation datasets promote methods that favor unspecific and broad functional classes over more informative and specific classes. We argue that this can bias the development of automated function prediction methods. The PANNZER web server and source code are available at http://ekhidna2.biocenter.helsinki.fi/sanspanz/. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

17. MOESM1 of The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author

Naihui Zhou, Yuxiang Jiang, Bergquist, Timothy, Lee, Alexandra, Balint Kacsoh, Crocker, Alex, Lewis, Kimberley, Georghiou, George, Nguyen, Huy, Md Nafiz Hamid, Davis, Larry, Tunca Dogan, Atalay, Volkan, Rifaioglu, Ahmet, Dalkıran, Alperen, Rengul Cetin Atalay, Chengxin Zhang, Hurto, Rebecca, Freddolino, Peter, Zhang, Yang, Prajwal Bhat, Supek, Fran, Fernández, José, Gemovic, Branislava, Perovic, Vladimir, Davidović, Radoslav, Sumonja, Neven, Veljkovic, Nevena, Ehsaneddin Asgari, Mofrad, Mohammad, Profiti, Giuseppe, Castrense Savojardo, Martelli, Pier Luigi, Casadio, Rita, Boecker, Florian, Schoof, Heiko, Indika Kahanda, Thurlby, Natalie, McHardy, Alice, Renaux, Alexandre, Saidi, Rabie, Gough, Julian, Freitas, Alex, Antczak, Magdalena, Fabris, Fabio, Wass, Mark, Hou, Jie, Jianlin Cheng, Wang, Zheng, Romero, Alfonso, Paccanaro, Alberto, Haixuan Yang, Goldberg, Tatyana, Chenguang Zhao, Holm, Liisa, Törönen, Petri, Medlar, Alan, Zosa, Elaine, Borukhov, Itamar, Novikov, Ilya, Wilkins, Angela, Lichtarge, Olivier, Po-Han Chi, Tseng, Wei-Cheng, Linial, Michal, Rose, Peter, Dessimoz, Christophe, Vidulin, Vedrana, Saso Dzeroski, Sillitoe, Ian, Sayoni Das, Lees, Jonathan Gill, Jones, David, Wan, Cen, Cozzetto, Domenico, Fa, Rui, Torres, Mateo, Vesztrocy, Alex Warwick, Rodriguez, Jose Manuel, Tress, Michael, Frasca, Marco, Notaro, Marco, Grossi, Giuliano, Petrini, Alessandro, Re, Matteo, Valentini, Giorgio, Mesiti, Marco, Roche, Daniel, Reeb, Jonas, Ritchie, David, Sabeur Aridhi, Alborzi, Seyed Ziaeddin, Marie-Dominique Devignes, Koo, Da Chen Emily, Bonneau, Richard, Gligorijević, Vladimir, Meet Barot, Fang, Hai, Toppo, Stefano, Lavezzo, Enrico, Falda, Marco, Berselli, Michele, Tosatto, Silvio, Carraro, Marco, Piovesan, Damiano, Hafeez Ur Rehman, Qizhong Mao, Shanshan Zhang, Vucetic, Slobodan, Black, Gage, Jo, Dane, Suh, Erica, Dayton, Jonathan, Larsen, Dallas, Omdahl, Ashton, McGuffin, Liam, Brackenridge, Danielle, Babbitt, Patricia, Yunes, Jeffrey, Fontana, Paolo, Zhang, Feng, Shanfeng Zhu, Ronghui You, Zihan Zhang, Suyang Dai, Shuwei Yao, Weidong Tian, Renzhi Cao, Chandler, Caleb, Amezola, Miguel, Johnson, Devon, Chang, Jia-Ming, Wen-Hung Liao, Liu, Yi-Wei, Pascarelli, Stefano, Yotam Frank, Hoehndorf, Robert, Kulmanov, Maxat, Boudellioua, Imane, Politano, Gianfranco, Carlo, Stefano Di, Benso, Alfredo, Hakala, Kai, Ginter, Filip, Mehryary, Farrokh, Suwisa Kaewphan, Björne, Jari, Moen, Hans, Tolvanen, Martti, Salakoski, Tapio, Kihara, Daisuke, Aashish Jain, Šmuc, Tomislav, Altenhoff, Adrian, Ben-Hur, Asa, Rost, Burkhard, Brenner, Steven, Orengo, Christine, Jeffery, Constance, Bosco, Giovanni, Hogan, Deborah, Martin, Maria, O’Donovan, Claire, Mooney, Sean, Greene, Casey, Radivojac, Predrag, and Friedberg, Iddo

Subjects
Pharmacology, FOS: Biological sciences, Data_FILES, Genetics, Biochemistry, Molecular Biology, 69999 Biological Sciences not elsewhere classified, Developmental Biology
Abstract

Additional file 1 Additional figures and tables referenced in the article.

Published
2019
Full Text
View/download PDF

19. The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author

Zhou, Naihui, primary, Jiang, Yuxiang, additional, Bergquist, Timothy R, additional, Lee, Alexandra J, additional, Kacsoh, Balint Z, additional, Crocker, Alex W, additional, Lewis, Kimberley A, additional, Georghiou, George, additional, Nguyen, Huy N, additional, Hamid, Md Nafiz, additional, Davis, Larry, additional, Dogan, Tunca, additional, Atalay, Volkan, additional, Rifaioglu, Ahmet S, additional, Dalkiran, Alperen, additional, Cetin-Atalay, Rengul, additional, Zhang, Chengxin, additional, Hurto, Rebecca L, additional, Freddolino, Peter L, additional, Zhang, Yang, additional, Bhat, Prajwal, additional, Supek, Fran, additional, Fernández, José M, additional, Gemovic, Branislava, additional, Perovic, Vladimir R, additional, Davidović, Radoslav S, additional, Sumonja, Neven, additional, Veljkovic, Nevena, additional, Asgari, Ehsaneddin, additional, Mofrad, Mohammad RK, additional, Profiti, Giuseppe, additional, Savojardo, Castrense, additional, Martelli, Pier Luigi, additional, Casadio, Rita, additional, Boecker, Florian, additional, Kahanda, Indika, additional, Thurlby, Natalie, additional, McHardy, Alice C, additional, Renaux, Alexandre, additional, Saidi, Rabie, additional, Gough, Julian, additional, Freitas, Alex A, additional, Antczak, Magdalena, additional, Fabris, Fabio, additional, Wass, Mark N, additional, Hou, Jie, additional, Cheng, Jianlin, additional, Wang, Zheng, additional, Romero, Alfonso E, additional, Paccanaro, Alberto, additional, Yang, Haixuan, additional, Goldberg, Tatyana, additional, Zhao, Chenguang, additional, Holm, Liisa, additional, Törönen, Petri, additional, Medlar, Alan J, additional, Zosa, Elaine, additional, Borukhov, Itamar, additional, Novikov, Ilya, additional, Wilkins, Angela, additional, Lichtarge, Olivier, additional, Chi, Po-Han, additional, Tseng, Wei-Cheng, additional, Linial, Michal, additional, Rose, Peter W, additional, Dessimoz, Christophe, additional, Vidulin, Vedrana, additional, Dzeroski, Saso, additional, Sillitoe, Ian, additional, Das, Sayoni, additional, Lees, Jonathan Gill, additional, Jones, David T, additional, Wan, Cen, additional, Cozzetto, Domenico, additional, Fa, Rui, additional, Torres, Mateo, additional, Vesztrocy, Alex Wiarwick, additional, Rodriguez, Jose Manuel, additional, Tress, Michael L, additional, Frasca, Marco, additional, Notaro, Marco, additional, Grossi, Giuliano, additional, Petrini, Alessandro, additional, Re, Matteo, additional, Valentini, Giorgio, additional, Mesiti, Marco, additional, Roche, Daniel B, additional, Reeb, Jonas, additional, Ritchie, David W, additional, Aridhi, Sabeur, additional, Alborzi, Seyed Ziaeddin, additional, Devignes, Marie-Dominique, additional, Emily Koo, Da Chen, additional, Bonneau, Richard, additional, Gligorijević, Vladimir, additional, Barot, Meet, additional, Fang, Hai, additional, Toppo, Stefano, additional, Lavezzo, Enrico, additional, Falda, Marco, additional, Berselli, Michele, additional, Tosatto, Silvio CE, additional, Carraro, Marco, additional, Piovesan, Damiano, additional, Rehman, Hafeez Ur, additional, Mao, Qizhong, additional, Zhang, Shanshan, additional, Vucetic, Slobodan, additional, Black, Gage S, additional, Jo, Dane, additional, Larsen, Dallas J, additional, Omdahl, Ashton R, additional, Sagers, Luke W, additional, Suh, Erica, additional, Dayton, Jonathan B, additional, McGuffin, Liam J, additional, Brackenridge, Danielle A, additional, Babbitt, Patricia C, additional, Yunes, Jeffrey M, additional, Fontana, Paolo, additional, Zhang, Feng, additional, Zhu, Shanfeng, additional, You, Ronghui, additional, Zhang, Zihan, additional, Dai, Suyang, additional, Yao, Shuwei, additional, Tian, Weidong, additional, Cao, Renzhi, additional, Chandler, Caleb, additional, Amezola, Miguel, additional, Johnson, Devon, additional, Chang, Jia-Ming, additional, Liao, Wen-Hung, additional, Liu, Yi-Wei, additional, Pascarelli, Stefano, additional, Frank, Yotam, additional, Hoehndorf, Robert, additional, Kulmanov, Maxat, additional, Boudellioua, Imane, additional, Politano, Gianfranco, additional, Di Carlo, Stefano, additional, Benso, Alfredo, additional, Hakala, Kai, additional, Ginter, Filip, additional, Mehryary, Farrokh, additional, Kaewphan, Suwisa, additional, Björne, Jari, additional, Moen, Hans, additional, Tolvanen, Martti E E, additional, Salakoski, Tapio, additional, Kihara, Daisuke, additional, Jain, Aashish, additional, Šmuc, Tomislav, additional, Altenhoff, Adrian, additional, Ben-Hur, Asa, additional, Rost, Burkhard, additional, Brenner, Steven E, additional, Orengo, Christine A, additional, Jeffery, Constance J, additional, Bosco, Giovanni, additional, Hogan, Deborah A, additional, Martin, Maria J, additional, O’Donovan, Claire, additional, Mooney, Sean D, additional, Greene, Casey S, additional, Radivojac, Predrag, additional, and Friedberg, Iddo, additional

Published
2019
Full Text
View/download PDF

24. Additional file 1 of An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Author

Yuxiang Jiang, Oron, Tal Ronnen, Clark, Wyatt T., Bankapur, Asma R., D’Andrea, Daniel, Lepore, Rosalba, Funk, Christopher S., Indika Kahanda, Verspoor, Karin M., Ben-Hur, Asa, Koo, Da Chen Emily, Penfold-Brown, Duncan, Shasha, Dennis, Youngs, Noah, Bonneau, Richard, Lin, Alexandra, Sahraeian, Sayed M. E., Martelli, Pier Luigi, Profiti, Giuseppe, Casadio, Rita, Renzhi Cao, Zhaolong Zhong, Jianlin Cheng, Altenhoff, Adrian, Skunca, Nives, Dessimoz, Christophe, Tunca Dogan, Hakala, Kai, Suwisa Kaewphan, Mehryary, Farrokh, Salakoski, Tapio, Ginter, Filip, Fang, Hai, Smithers, Ben, Oates, Matt, Gough, Julian, Törönen, Petri, Koskinen, Patrik, Holm, Liisa, Ching-Tai Chen, Hsu, Wen-Lian, Bryson, Kevin, Cozzetto, Domenico, Minneci, Federico, Jones, David T., Chapman, Samuel, Dukka BKC, Ishita K. Khan, Kihara, Daisuke, Ofer, Dan, Rappoport, Nadav, Stern, Amos, Cibrian-Uhalte, Elena, Denny, Paul, Foulger, Rebecca E., Hieta, Reija, Legge, Duncan, Lovering, Ruth C., Magrane, Michele, Melidoni, Anna N., Mutowo-Meullenet, Prudence, Pichler, Klemens, Shypitsyna, Aleksandra, Li, Biao, Pooya Zakeri, ElShal, Sarah, Léon-Charles Tranchevent, Sayoni Das, Dawson, Natalie L., Lee, David, Lees, Jonathan G., Sillitoe, Ian, Prajwal Bhat, Nepusz, Tamás, Romero, Alfonso E., Sasidharan, Rajkumar, Haixuan Yang, Paccanaro, Alberto, Gillis, Jesse, Sedeño-Cortés, Adriana E., Pavlidis, Paul, Feng, Shou, Cejuela, Juan M., Goldberg, Tatyana, Hamp, Tobias, Richter, Lothar, Salamov, Asaf, Gabaldon, Toni, Marcet-Houben, Marina, Supek, Fran, Qingtian Gong, Ning, Wei, Yuanpeng Zhou, Weidong Tian, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Toppo, Stefano, Ferrari, Carlo, Giollo, Manuel, Piovesan, Damiano, Tosatto, Silvio C.E., Pozo, Angela Del, Fernández, José M., Maietta, Paolo, Valencia, Alfonso, Tress, Michael L., Benso, Alfredo, Carlo, Stefano Di, Politano, Gianfranco, Savino, Alessandro, Hafeez Ur Rehman, Re, Matteo, Mesiti, Marco, Valentini, Giorgio, Bargsten, Joachim W., Dijk, Aalt D. J. Van, Gemovic, Branislava, Glisic, Sanja, Vladmir Perovic, Veljkovic, Veljko, Veljkovic, Nevena, Danillo C. Almeida-E-Silva, Vencio, Ricardo Z. N., Malvika Sharan, Vogel, Jörg, Lakesh Kansakar, Shanshan Zhang, Vucetic, Slobodan, Wang, Zheng, Sternberg, Michael J. E., Wass, Mark N., Huntley, Rachael P., Martin, Maria J., O’Donovan, Claire, Robinson, Peter N., Moreau, Yves, Tramontano, Anna, Babbitt, Patricia C., Brenner, Steven E., Linial, Michal, Orengo, Christine A., Rost, Burkhard, Greene, Casey S., Mooney, Sean D., Friedberg, Iddo, and Radivojac, Predrag

Abstract

A document containing a subset of CAFA2 analyses that are equivalent to those provided about the CAFA1 experiment in the CAFA1 supplement. (PDF 11100 kb)

Published
2016
Full Text
View/download PDF

25. Robust multi-group gene set analysis with few replicates

Author

University of Helsinki, Institute of Biotechnology, University of Helsinki, Department of Biosciences, Mishra, Pashupati P., Medlar, Alan, Holm, Liisa, Törönen, Petri, University of Helsinki, Institute of Biotechnology, University of Helsinki, Department of Biosciences, Mishra, Pashupati P., Medlar, Alan, Holm, Liisa, and Törönen, Petri

Abstract

Background: Competitive gene set analysis is a standard exploratory tool for gene expression data. Permutation-based competitive gene set analysis methods are preferable to parametric ones because the latter make strong statistical assumptions which are not always met. For permutation-based methods, we permute samples, as opposed to genes, as doing so preserves the inter-gene correlation structure. Unfortunately, up until now, sample permutation-based methods have required a minimum of six replicates per sample group. Results: We propose a new permutation-based competitive gene set analysis method for multi-group gene expression data with as few as three replicates per group. The method is based on advanced sample permutation technique that utilizes all groups within a data set for pairwise comparisons. We present a comprehensive evaluation of different permutation techniques, using multiple data sets and contrast the performance of our method, mGSZm, with other state of the art methods. We show that mGSZm is robust, and that, despite only using less than six replicates, we are able to consistently identify a high proportion of the top ranked gene sets from the analysis of a substantially larger data set. Further, we highlight other methods where performance is highly variable and appears dependent on the underlying data set being analyzed. Conclusions: Our results demonstrate that robust gene set analysis of multi-group gene expression data is permissible with as few as three replicates. In doing so, we have extended the applicability of such approaches to resource constrained experiments where additional data generation is prohibitively difficult or expensive. An R package implementing the proposed method and supplementary materials are available from the website http:// ekhidna.biocenter.helsinki.fi/downloads/pashupati/mGSZm.html.

Published
2016

28. Efficient gene set analysis of high-throughput data : From omics to pathway architecture of health and disease

Author

Mishra, Pashupati, University of Helsinki, Faculty of Biological and Environmental Sciences, Doctoral Programme in Integrative Life Science, Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Helsingin yliopisto, bio- ja ympäristötieteellinen tiedekunta, Integroivien biotieteiden tohtoriohjelma, Helsingfors universitet, bio- och miljövetenskapliga fakulteten, Doktorandprogrammet i integrerande biovetenskap, Brazma, Alvis, Holm, Liisa, Törönen, Petri, and Lehtimäki, Terho

Subjects
genetics
Abstract

Background: A wide range of diseases, normal variations in physiology and development of different species are caused by alterations in gene regulation. The study of gene expression is thus crucial for understanding both normal physiology and disease mechanisms. High-throughput mea- surement technologies allow the profiling of tens of thousands of genes simultaneously. However, the high volume of data thus generated poses methodological challenges in inferring biological consequences from gene expression changes. Traditional gene wise analysis of high dimensional data is overwhelming, prone to noise and unintuitive. The analysis of sets of genes (gene set analysis, GSA), solves the problem by boosting statistical power and biological interpretability. Despite more than a decade of research on gene set analysis, there are still serious limitations in the existing methods. Aims of the study: The objectives of this study were: (1) development of an efficient p-value estimation method for GSA; (2) development of an advanced permutation method for GSA of multi-group gene expression data with fewer replicates; and (3) implementation of the developed methods for the identification of novel smoking induced epigenetic signatures at biological pathway level. Materials and methods: The first study involved the assessment of four different statistical null models for modeling the distribution of gene set scores calculated with the Gene Set Z-score (GSZ) function from permuted gene expression data. A new GSA method - modified GSZ (mGSZ) - based on GSZ and the most optimal distribution model was developed. mGSZ was evaluated by comparing its results with seven other popular GSA methods using four different publicly available gene expression datasets. The second study involved the evaluation of six different permutation schemes for GSA of multi-group (more than two groups) datasets based on the identification of reference gene sets generated using a novel data splitting approach. A new GSA method based on a modification of mGSZ (mGSZm) was developed by implementing the best permutation method for the analysis of multi-group data with fewer than six replicates per group. mGSZm was evaluated by contrasting its performance with seven other state-of-the-art GSA methods suitable for multi-group data. The evaluation was based on three different publicly available multi-group datasets. The third study involved an implementation of mGSZ for GSA of genome-wide DNA methylation data from the Cardiovascular Risk in Young Finns study (YFS) cohort with gene sets downloaded from the Molecular Signature Database (MSigDB). Methylation measurements were done on a subset of 192 individuals from whole-blood samples from the 2011 follow-up study using Illumina Infinium HumanMethylation450 BeadChips. Results: Overall, efficient and robust GSA methods were developed (studies I-II) and implemented (study III). In study I, the results demonstrated a clear advantage of asymptotic p-value estimation over empirical methods. mGSZ, a GSA method based on asymptotic p-values, requires fewer permutations which speeds up the analysis process. mGSZ outperformed state-of-the-art methods based on three different evaluations with three different datasets. In study II, results from a novel evaluation approach with two different datasets suggested that the proposed advanced permutation method outperformed the naive permutation method in GSA of multi-group data with fewer than six replicates. Evaluation of mGSZm, a GSA method equipped with the advanced permutation method and asymptotic n/a

Published
2020

29. An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Author

Yuxiang Jiang, Tal Ronnen Oron, Wyatt T. Clark, Asma R. Bankapur, Daniel D’Andrea, Rosalba Lepore, Christopher S. Funk, Indika Kahanda, Karin M. Verspoor, Asa Ben-Hur, Da Chen Emily Koo, Duncan Penfold-Brown, Dennis Shasha, Noah Youngs, Richard Bonneau, Alexandra Lin, Sayed M. E. Sahraeian, Pier Luigi Martelli, Giuseppe Profiti, Rita Casadio, Renzhi Cao, Zhaolong Zhong, Jianlin Cheng, Adrian Altenhoff, Nives Skunca, Christophe Dessimoz, Tunca Dogan, Kai Hakala, Suwisa Kaewphan, Farrokh Mehryary, Tapio Salakoski, Filip Ginter, Hai Fang, Ben Smithers, Matt Oates, Julian Gough, Petri Törönen, Patrik Koskinen, Liisa Holm, Ching-Tai Chen, Wen-Lian Hsu, Kevin Bryson, Domenico Cozzetto, Federico Minneci, David T. Jones, Samuel Chapman, Dukka BKC, Ishita K. Khan, Daisuke Kihara, Dan Ofer, Nadav Rappoport, Amos Stern, Elena Cibrian-Uhalte, Paul Denny, Rebecca E. Foulger, Reija Hieta, Duncan Legge, Ruth C. Lovering, Michele Magrane, Anna N. Melidoni, Prudence Mutowo-Meullenet, Klemens Pichler, Aleksandra Shypitsyna, Biao Li, Pooya Zakeri, Sarah ElShal, Léon-Charles Tranchevent, Sayoni Das, Natalie L. Dawson, David Lee, Jonathan G. Lees, Ian Sillitoe, Prajwal Bhat, Tamás Nepusz, Alfonso E. Romero, Rajkumar Sasidharan, Haixuan Yang, Alberto Paccanaro, Jesse Gillis, Adriana E. Sedeño-Cortés, Paul Pavlidis, Shou Feng, Juan M. Cejuela, Tatyana Goldberg, Tobias Hamp, Lothar Richter, Asaf Salamov, Toni Gabaldon, Marina Marcet-Houben, Fran Supek, Qingtian Gong, Wei Ning, Yuanpeng Zhou, Weidong Tian, Marco Falda, Paolo Fontana, Enrico Lavezzo, Stefano Toppo, Carlo Ferrari, Manuel Giollo, Damiano Piovesan, Silvio C.E. Tosatto, Angela del Pozo, José M. Fernández, Paolo Maietta, Alfonso Valencia, Michael L. Tress, Alfredo Benso, Stefano Di Carlo, Gianfranco Politano, Alessandro Savino, Hafeez Ur Rehman, Matteo Re, Marco Mesiti, Giorgio Valentini, Joachim W. Bargsten, Aalt D. J. van Dijk, Branislava Gemovic, Sanja Glisic, Vladmir Perovic, Veljko Veljkovic, Nevena Veljkovic, Danillo C. Almeida-e-Silva, Ricardo Z. N. Vencio, Malvika Sharan, Jörg Vogel, Lakesh Kansakar, Shanshan Zhang, Slobodan Vucetic, Zheng Wang, Michael J. E. Sternberg, Mark N. Wass, Rachael P. Huntley, Maria J. Martin, Claire O’Donovan, Peter N. Robinson, Yves Moreau, Anna Tramontano, Patricia C. Babbitt, Steven E. Brenner, Michal Linial, Christine A. Orengo, Burkhard Rost, Casey S. Greene, Sean D. Mooney, Iddo Friedberg, Predrag Radivojac, Jiang, Yuxiang, Oron, Tal Ronnen, Clark, Wyatt T., Bankapur, Asma R., D’Andrea, Daniel, Lepore, Rosalba, Funk, Christopher S., Kahanda, Indika, Verspoor, Karin M., Ben-Hur, Asa, Koo, Da Chen Emily, Penfold-Brown, Duncan, Shasha, Denni, Youngs, Noah, Bonneau, Richard, Lin, Alexandra, Sahraeian, Sayed M. E., Martelli, Pier Luigi, Profiti, Giuseppe, Casadio, Rita, Cao, Renzhi, Zhong, Zhaolong, Cheng, Jianlin, Altenhoff, Adrian, Skunca, Nive, Dessimoz, Christophe, Dogan, Tunca, Hakala, Kai, Kaewphan, Suwisa, Mehryary, Farrokh, Salakoski, Tapio, Ginter, Filip, Fang, Hai, Smithers, Ben, Oates, Matt, Gough, Julian, Törönen, Petri, Koskinen, Patrik, Holm, Liisa, Chen, Ching-Tai, Hsu, Wen-Lian, Bryson, Kevin, Cozzetto, Domenico, Minneci, Federico, Jones, David T., Chapman, Samuel, Bkc, Dukka, Khan, Ishita K., Kihara, Daisuke, Ofer, Dan, Rappoport, Nadav, Stern, Amo, Cibrian-Uhalte, Elena, Denny, Paul, Foulger, Rebecca E., Hieta, Reija, Legge, Duncan, Lovering, Ruth C., Magrane, Michele, Melidoni, Anna N., Mutowo-Meullenet, Prudence, Pichler, Klemen, Shypitsyna, Aleksandra, Li, Biao, Zakeri, Pooya, Elshal, Sarah, Tranchevent, Léon-Charle, Das, Sayoni, Dawson, Natalie L., Lee, David, Lees, Jonathan G., Sillitoe, Ian, Bhat, Prajwal, Nepusz, Tamá, Romero, Alfonso E., Sasidharan, Rajkumar, Yang, Haixuan, Paccanaro, Alberto, Gillis, Jesse, Sedeño-Cortés, Adriana E., Pavlidis, Paul, Feng, Shou, Cejuela, Juan M., Goldberg, Tatyana, Hamp, Tobia, Richter, Lothar, Salamov, Asaf, Gabaldon, Toni, Marcet-Houben, Marina, Supek, Fran, Gong, Qingtian, Ning, Wei, Zhou, Yuanpeng, Tian, Weidong, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Toppo, Stefano, Ferrari, Carlo, Giollo, Manuel, Piovesan, Damiano, Tosatto, Silvio C.E., del Pozo, Angela, Fernández, José M., Maietta, Paolo, Valencia, Alfonso, Tress, Michael L., Benso, Alfredo, Di Carlo, Stefano, Politano, Gianfranco, Savino, Alessandro, Rehman, Hafeez Ur, Re, Matteo, Mesiti, Marco, Valentini, Giorgio, Bargsten, Joachim W., van Dijk, Aalt D. J., Gemovic, Branislava, Glisic, Sanja, Perovic, Vladmir, Veljkovic, Veljko, Veljkovic, Nevena, Almeida-e-Silva, Danillo C., Vencio, Ricardo Z. N., Sharan, Malvika, Vogel, Jörg, Kansakar, Lakesh, Zhang, Shanshan, Vucetic, Slobodan, Wang, Zheng, Sternberg, Michael J. E., Wass, Mark N., Huntley, Rachael P., Martin, Maria J., O’Donovan, Claire, Robinson, Peter N., Moreau, Yve, Tramontano, Anna, Babbitt, Patricia C., Brenner, Steven E., Linial, Michal, Orengo, Christine A., Rost, Burkhard, Greene, Casey S., Mooney, Sean D., Friedberg, Iddo, Radivojac, Predrag, Friedberg, Iddo [0000-0002-1789-8000], Apollo - University of Cambridge Repository, (ukupan broj autora: 147), Biotechnology and Biological Sciences Research Council (BBSRC), National Science Foundation (Estados Unidos), United States of Department of Health & Human Services, National Natural Science Foundation of China, Natural Sciences and Engineering Research Council (Canadá), São Paulo Research Foundation, Ministerio de Economía y Competitividad (España), Biotechnology and Biological Sciences Research Council (Reino Unido), Katholieke Universiteit Leuven (Bélgica), Newton International Fellowship Scheme of the Royal Society grant, British Heart Foundation, Ministry of Education, Science and Technological Development (Serbia), Office of Biological and Environmental Research (Estados Unidos), Australian Research Council, University of Padua (Italia), Swiss National Science Foundation, Institute of Biotechnology, Computational genomics, and Bioinformatics

Subjects
0301 basic medicine, Computer science, Disease gene prioritization, Protein function prediction, Ecology, Evolution, Behavior and Systematics, Genetics, Cell Biology, 05 Environmental Sciences, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, computer.software_genre, Quantitative Biology - Quantitative Methods, Wiskundige en Statistische Methoden - Biometris, Field (computer science), Laboratorium voor Plantenveredeling, Function (engineering), Databases, Protein, 1183 Plant biology, microbiology, virology, Quantitative Methods (q-bio.QM), media_common, Genetics & Heredity, Settore BIO/11 - BIOLOGIA MOLECOLARE, Ecology, SISTA, 1184 Genetics, developmental biology, physiology, Life Sciences & Biomedicine, Algorithms, Bioinformatics, Evolution, media_common.quotation_subject, BIOINFORMÁTICA, Machine learning, Bottleneck, Set (abstract data type), BIOS Applied Bioinformatics, 03 medical and health sciences, Annotation, Structure-Activity Relationship, Behavior and Systematics, Human Phenotype Ontology, Humans, ddc:610, DISINTEGRIN, Mathematical and Statistical Methods - Biometris, BIOINFORMATICS, 08 Information And Computing Sciences, Science & Technology, business.industry, Research, ADAM, Proteins, Computational Biology, Molecular Sequence Annotation, 06 Biological Sciences, Data set, ONTOLOGY, Plant Breeding, 030104 developmental biology, Gene Ontology, Biotechnology & Applied Microbiology, FOS: Biological sciences, Artificial intelligence, business, computer, Software
Abstract

BACKGROUND: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. RESULTS: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. CONCLUSIONS: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent., We acknowledge the contributions of Maximilian Hecht, Alexander Grün, Julia Krumhoff, My Nguyen Ly, Jonathan Boidol, Rene Schoeffel, Yann Spöri, Jessika Binder, Christoph Hamm and Karolina Worf. This work was partially supported by the following grants: National Science Foundation grants DBI-1458477 (PR), DBI-1458443 (SDM), DBI-1458390 (CSG), DBI-1458359 (IF), IIS-1319551 (DK), DBI-1262189 (DK), and DBI-1149224 (JC); National Institutes of Health grants R01GM093123 (JC), R01GM097528 (DK), R01GM076990 (PP), R01GM071749 (SEB), R01LM009722 (SDM), and UL1TR000423 (SDM); the National Natural Science Foundation of China grants 3147124 (WT) and 91231116 (WT); the National Basic Research Program of China grant 2012CB316505 (WT); NSERC grant RGPIN 371348-11 (PP); FP7 infrastructure project TransPLANT Award 283496 (ADJvD); Microsoft Research/FAPESP grant 2009/53161-6 and FAPESP fellowship 2010/50491-1 (DCAeS); Biotechnology and Biological Sciences Research Council grants BB/L020505/1 (DTJ), BB/F020481/1 (MJES), BB/K004131/1 (AP), BB/F00964X/1 (AP), and BB/L018241/1 (CD); the Spanish Ministry of Economics and Competitiveness grant BIO2012-40205 (MT); KU Leuven CoE PFV/10/016 SymBioSys (YM); the Newton International Fellowship Scheme of the Royal Society grant NF080750 (TN). CSG was supported in part by the Gordon and Betty Moore Foundation’s Data-Driven Discovery Initiative grant GBMF4552. Computational resources were provided by CSC – IT Center for Science Ltd., Espoo, Finland (TS). This work was supported by the Academy of Finland (TS). RCL and ANM were supported by British Heart Foundation grant RG/13/5/30112. PD, RCL, and REF were supported by Parkinson’s UK grant G-1307, the Alexander von Humboldt Foundation through the German Federal Ministry for Education and Research, Ernst Ludwig Ehrlich Studienwerk, and the Ministry of Education, Science and Technological Development of the Republic of Serbia grant 173001. This work was a Technology Development effort for ENIGMA – Ecosystems and Networks Integrated with Genes and Molecular Assemblies (http://enigma.lbl.gov), a Scientific Focus Area Program at Lawrence Berkeley National Laboratory, which is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Biological & Environmental Research grant DE-AC02-05CH11231. ENIGMA only covers the application of this work to microbial proteins. NSF DBI-0965616 and Australian Research Council grant DP150101550 (KMV). NSF DBI-0965768 (ABH). NIH T15 LM00945102 (training grant for CSF). FP7 FET grant MAESTRA ICT-2013-612944 and FP7 REGPOT grant InnoMol (FS). NIH R01 GM60595 (PCB). University of Padova grants CPDA138081/13 (ST) and GRIC13AAI9 (EL). Swiss National Science Foundation grant 150654 and UK BBSRC grant BB/M015009/1 (COD). PRB2 IPT13/0001 - ISCIII-SGEFI / FEDER (JMF)., This is the final version of the article. It first appeared from BioMed Central at http://dx.doi.org/10.1186/s13059-016-1037-6.

Published
2016

30. Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis.

Author

Pussila M, Laiho A, Törönen P, Björkbacka P, Nykänen S, Pylvänäinen K, Holm L, Mecklin JP, Renkonen-Sinisalo L, Lehtonen T, Lepistö A, Linden J, Mäki-Nevala S, Peltomäki P, and Nyström M

Subjects
Humans, Female, Male, Middle Aged, Mutation, Adult, Aged, MutL Protein Homolog 1 genetics, Gene Expression Profiling, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms etiology, Carcinogenesis genetics, DNA Mismatch Repair genetics, Transcriptome, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, Colorectal Neoplasms, Hereditary Nonpolyposis complications, Microsatellite Instability, Mitosis genetics
Abstract

Background: Lynch syndrome (LS) is one of the most common hereditary cancer syndromes worldwide. Dominantly inherited mutation in one of four DNA mismatch repair genes combined with somatic events leads to mismatch repair deficiency and microsatellite instability (MSI) in tumours. Due to a high lifetime risk of cancer, regular surveillance plays a key role in cancer prevention; yet the observation of frequent interval cancers points to insufficient cancer prevention by colonoscopy-based methods alone. This study aimed to identify precancerous functional changes in colonic mucosa that could facilitate the monitoring and prevention of cancer development in LS., Methods: The study material comprised colon biopsy specimens (n = 71) collected during colonoscopy examinations from LS carriers (tumour-free, or diagnosed with adenoma, or diagnosed with carcinoma) and a control group, which included sporadic cases without LS or neoplasia. The majority (80%) of LS carriers had an inherited genetic MLH1 mutation. The remaining 20% included MSH2 mutation carriers (13%) and MSH6 mutation carriers (7%). The transcriptomes were first analysed with RNA-sequencing and followed up with Gorilla Ontology analysis and Reactome Knowledgebase and Ingenuity Pathway Analyses to detect functional changes that might be associated with the initiation of the neoplastic process in LS individuals., Findings: With pathway and gene ontology analyses combined with measurement of mitotic perimeters from colonic mucosa and tumours, we found an increased tendency to chromosomal instability (CIN), already present in macroscopically normal LS mucosa. Our results suggest that CIN is an earlier aberration than MSI and may be the initial cancer driving aberration, whereas MSI accelerates tumour formation. Furthermore, our results suggest that MLH1 deficiency plays a significant role in the development of CIN., Interpretation: The results validate our previous findings from mice and highlight early mitotic abnormalities as an important contributor and precancerous marker of colorectal tumourigenesis in LS., Funding: This work was supported by grants from the Jane and Aatos Erkko Foundation, the Academy of Finland (330606 and 331284), Cancer Foundation Finland sr, and the Sigrid Jusélius Foundation. Open access is funded by Helsinki University Library., Competing Interests: Declaration of interests Minna Nyström is a member of the board of directors and a shareholder in LS CancerDiag Ltd. No disclosures were reported by the other authors., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
Full Text
View/download PDF

31. DALI shines a light on remote homologs: One hundred discoveries.

Author

Holm L, Laiho A, Törönen P, and Salgado M

Subjects
Databases, Protein, Sequence Alignment, Protein Domains, Protein Structure, Secondary, Proteins chemistry
Abstract

Structural comparison reveals remote homology that often fails to be detected by sequence comparison. The DALI web server (http://ekhidna2.biocenter.helsinki.fi/dali) is a platform for structural analysis that provides database searches and interactive visualization, including structural alignments annotated with secondary structure, protein families and sequence logos, and 3D structure superimposition supported by color-coded sequence and structure conservation. Here, we are using DALI to mine the AlphaFold Database version 1, which increased the structural coverage of protein families by 20%. We found 100 remote homologous relationships hitherto unreported in the current reference database for protein domains, Pfam 35.0. In particular, we linked 35 domains of unknown function (DUFs) to the previously characterized families, generating a functional hypothesis that can be explored downstream in structural biology studies. Other findings include gene fusions, tandem duplications, and adjustments to domain boundaries. The evidence for homology can be browsed interactively through live examples on DALI's website., (© 2022 The Protein Society.)

Published
2023
Full Text
View/download PDF

32. PANNZER-A practical tool for protein function prediction.

Author

Törönen P and Holm L

Subjects
Algorithms, Computational Biology, Databases, Protein, Molecular Sequence Annotation, Proteins chemistry, Proteins genetics, Software
Abstract

The facility of next-generation sequencing has led to an explosion of gene catalogs for novel genomes, transcriptomes and metagenomes, which are functionally uncharacterized. Computational inference has emerged as a necessary substitute for first-hand experimental evidence. PANNZER (Protein ANNotation with Z-scoRE) is a high-throughput functional annotation web server that stands out among similar publically accessible web servers in supporting submission of up to 100,000 protein sequences at once and providing both Gene Ontology (GO) annotations and free text description predictions. Here, we demonstrate the use of PANNZER and discuss future plans and challenges. We present two case studies to illustrate problems related to data quality and method evaluation. Some commonly used evaluation metrics and evaluation datasets promote methods that favor unspecific and broad functional classes over more informative and specific classes. We argue that this can bias the development of automated function prediction methods. The PANNZER web server and source code are available at http://ekhidna2.biocenter.helsinki.fi/sanspanz/., (© 2021 The Protein Society.)

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results