Browsing by Subject "LIBRARY"

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  • Ravikumar, Balaguru; Timonen, Sanna; Alam, Zaid; Parri, Elina; Wennerberg, Krister; Aittokallio, Tero (2019)
    Owing to the intrinsic polypharmacological nature of most small-molecule kinase inhibitors, there is a need for computational models that enable systematic exploration of the chemogenomic landscape underlying druggable kinome toward more efficient kinome-profiling strategies. We implemented Virtual-KinomeProfiler, an efficient computational platform that captures distinct representations of chemical similarity space of the druggable kinome for various drug discovery endeavors. By using the computational platform, we profiled approximately 37 million compound-kinase pairs and made predictions for 151,708 compounds in terms of their repositioning and lead molecule potential, against 248 kinases simultaneously. Experimental testing with biochemical assays validated 51 of the predicted interactions, identifying 19 small-molecule inhibitors of EGFR, HCK, FLT1, and MSK1 protein kinases. The prediction model led to a 1.5-fold increase in precision and 2.8-fold decrease in false-discovery rate, when compared with traditional single-dose biochemical screening, which demonstrates its potential to drastically expedite the kinome-specific drug discovery process.
  • DDD Study; Konrad, Enrico D. H.; Nardini, Niels; Kuismin, Outi; Kurki, Mitja I.; Pietiläinen, Olli; Palotie, Aarno (2019)
    Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.
  • Saarti, Jarmo; Tuominen, Kimmo (2020)
    Purpose Although resource sharing between scholars is evolving rapidly, This paper uses paper-based interlibrary lending (ILL) procedures in the service repertoire of academic libraries. However, the current business model of acquiring toll-access journals and e-books does not seem to fit very well with traditional ILL practices. In addition, the new models of peer-to-peer resource sharing between academics seem to be much more effective than ILL. Scholars arrange access to the needed publications by using legal (buying, exchanging) and illegal means (Sci-Hub, etc.). Furthermore, the demands for open access have increased, voiced not only by librarians and science funders but also by politicians. This development might change the scholarly publication ecosystem, even though older publications are still likely to remain closed. Design/methodology/approach This paper contrasts the ILL and usage statistics of Finnish university libraries with the use of ResearchGate, a popular academic social network, which we treat as an example of a peer-to-peer sharing service. Findings Based on the data, there seems to be a change of paradigm in the resource sharing: the traditional ILL seems to be decreasing and becoming more like a niche service and the digital use and use of social media peer-to-peer resource sharing applications seem to increase rapidly. Originality/value The paper examines current resource sharing trends. The analysis is based on the data of Finnish resource sharing, interlibrary lending and ResearchGate usage.
  • Tonkin-Hill, Gerry; MacAlasdair, Neil; Ruis, Christopher; Weimann, Aaron; Horesh, Gal; Lees, John A.; Gladstone, Rebecca A.; Lo, Stephanie; Beaudoin, Christopher; Floto, R. Andres; Frost, Simon D. W.; Corander, Jukka; Bentley, Stephen D.; Parkhill, Julian (2020)
    Population-level comparisons of prokaryotic genomes must take into account the substantial differences in gene content resulting from horizontal gene transfer, gene duplication and gene loss. However, the automated annotation of prokaryotic genomes is imperfect, and errors due to fragmented assemblies, contamination, diverse gene families and mis-assemblies accumulate over the population, leading to profound consequences when analysing the set of all genes found in a species. Here, we introduce Panaroo, a graph-based pangenome clustering tool that is able to account for many of the sources of error introduced during the annotation of prokaryotic genome assemblies. Panaroo is available at
  • Salmela, Elina; Lappalainen, Tuuli; Liu, Jianjun; Sistonen, Pertti; Andersen, Peter M.; Schreiber, Stefan; Savontaus, Marja-Liisa; Czene, Kamila; Lahermo, Päivi; Hall, Per; Kere, Juha (2011)
  • Carney, Randy P.; Hazari, Sidhartha; Rojalin, Tatu; Knudson, Alisha; Gao, Tingjuan; Tang, Yuchen; Liu, Ruiwu; Viitala, Tapani; Yliperttula, Marjo; Lam, Kit S. (2017)
    All cells expel a variety of nanosized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application, yet it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here, peptide binding to tumor-associated EVs via overexpressed membrane protein is demonstrated. It is found that SKOV-3 ovarian tumor cells and their released EVs express alpha(3)beta(1) integrin, which can be targeted by the in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enables the differentiation of cancer-associated exosomes from noncancer exosomes. Furthermore, the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30 is introduced. LXY30 not only exhibits high specificity and affinity to alpha(3)beta(1) integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
  • 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.; Dalkiran, Alperen; Atalay, Rengul Cetin; Zhang, Chengxin; Hurto, Rebecca L.; Freddolino, Peter L.; Zhang, Yang; Bhat, Prajwal; Supek, Fran; Fernandez, Jose M.; Gemovic, Branislava; Perovic, Vladimir R.; Davidovic, Radoslav S.; Sumonja, Neven; Veljkovic, Nevena; Asgari, Ehsaneddin; Mofrad, Mohammad R. K.; 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; Vesztrocy, Alex Warwick; 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; Gligorijevic, Vladimir; Barot, Meet; Fang, Hai; Toppo, Stefano; Lavezzo, Enrico; Falda, Marco; Berselli, Michele; Tosatto, Silvio C. E.; Carraro, Marco; Piovesan, Damiano; Rehman, Hafeez Ur; Mao, Qizhong; Zhang, Shanshan; Vucetic, Slobodan; Black, Gage S.; Jo, Dane; Suh, Erica; Dayton, Jonathan B.; Larsen, Dallas J.; Omdahl, Ashton R.; McGuffin, Liam J.; Brackenridge, Danielle A.; Babbitt, Patricia C.; Yunes, Jeffrey M.; Fontana, Paolo; Zhang, Feng; Zhu, Shanfeng; You, Ronghui; Zhang, Zihan; Dai, Suyang; Yao, Shuwei; Tian, Weidong; Cao, Renzhi; Chandler, Caleb; Amezola, Miguel; Johnson, Devon; Chang, Jia-Ming; Liao, Wen-Hung; Liu, Yi-Wei; Pascarelli, Stefano; Frank, Yotam; Hoehndorf, Robert; Kulmanov, Maxat; Boudellioua, Imane; Politano, Gianfranco; Di Carlo, Stefano; Benso, Alfredo; Hakala, Kai; Ginter, Filip; Mehryary, Farrokh; Kaewphan, Suwisa; Bjorne, Jari; Moen, Hans; Tolvanen, Martti E. E.; Salakoski, Tapio; Kihara, Daisuke; Jain, Aashish; Smuc, Tomislav; Altenhoff, Adrian; Ben-Hur, Asa; Rost, Burkhard; Brenner, Steven E.; Orengo, Christine A.; Jeffery, Constance J.; Bosco, Giovanni; Hogan, Deborah A.; Martin, Maria J.; O'Donovan, Claire; Mooney, Sean D.; Greene, Casey S.; Radivojac, Predrag; Friedberg, Iddo (2019)
    Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, 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. Conclusion We 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.