IDPpi:Protein-protein interaction analyses of human intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) are characterized by the lack of a fixed tertiary structure and are involved in the regulation of key biological processes via binding to multiple protein partners. IDPs are malleable, adapting to structurally different partners, and this flexibility stems from features encoded in the primary structure. The assumption that universal sequence information will facilitate coverage of the sparse zones of the human interactome motivated us to explore the possibility of predicting protein-protein interactions (PPIs) that involve IDPs based on sequence characteristics. We developed a method that relies on features of the interacting and non-interacting protein pairs and utilizes machine learning to classify and predict IDP PPIs. Consideration of both sequence determinants specific for conformational organizations and the multiplicity of IDP interactions in the training phase ensured a reliable approach that is superior to current state-of-the-art methods. By applying a strict evaluation procedure, we confirm that our method predicts interactions of the IDP of interest even on the proteome-scale. This service is provided as a web tool to expedite the discovery of new interactions and IDP functions with enhanced efficiency. © 2018 The Author(s)

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

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 aeruginosa 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

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

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.Peer reviewe

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

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.</p

Suočavanje sa smrću

Problem smrti i umiranja prisutan je u brojnim djelima, a predmet je i mnogih znanstvenih istraživanja. Ljudi od pamtivijeka pokušavaju razumjeti smrt i ono što dolazi nakon nje, posvećivali su joj slike, pisana i usmena djela koja su se prenosila na daljnje generacije stvarajući temelje i okvire misli i spoznaja o smrti. Biološki je smrt gotovo jasna i nije tajna da sve što se rodi treba i umrijeti te sve što započne, jednom mora i završiti, no smrt i umiranje, kraj kao takav, emocionalno su neprihvatljivi i ljudi se teško suočavaju sa spoznajom da se njima ili njima bliskim osobama bliži kraj. Smrt označava ograničenost života, spoznaju da ništa nije vječno i da život nastavlja svojim tokom i nakon nas. Suočiti se sa smrću je današnjem čovjeku iznimno psihički zahtjevno, zato koristi brojne mehanizme kojima želi umanjiti strah, osjećaj bespomoćnosti i ograničenosti i na neki način pobjeći od smrti. Bori se svim načinima pronaći formulu za vječnost i besmrtnost. U susretu sa smrću služimo se brojnim mehanizmima kojima se pokušavamo obraniti od negacije, identifikacije, introjekcije i drugog. (1) S obzirom da se zdravstveni djelatnici vrlo često susreću sa smrću, edukacija na temu suočavanja sa smrću iznimno je važna i neophodna kako bi olakšali prihvaćanje smrti umirućim pacijentima, članovima njihove obitelji, ali i kako bi osnažili i zaštitili sami sebe u suočavanju s takvim situacijama

Suočavanje sa smrću

Problem smrti i umiranja prisutan je u brojnim djelima, a predmet je i mnogih znanstvenih istraživanja. Ljudi od pamtivijeka pokušavaju razumjeti smrt i ono što dolazi nakon nje, posvećivali su joj slike, pisana i usmena djela koja su se prenosila na daljnje generacije stvarajući temelje i okvire misli i spoznaja o smrti. Biološki je smrt gotovo jasna i nije tajna da sve što se rodi treba i umrijeti te sve što započne, jednom mora i završiti, no smrt i umiranje, kraj kao takav, emocionalno su neprihvatljivi i ljudi se teško suočavaju sa spoznajom da se njima ili njima bliskim osobama bliži kraj. Smrt označava ograničenost života, spoznaju da ništa nije vječno i da život nastavlja svojim tokom i nakon nas. Suočiti se sa smrću je današnjem čovjeku iznimno psihički zahtjevno, zato koristi brojne mehanizme kojima želi umanjiti strah, osjećaj bespomoćnosti i ograničenosti i na neki način pobjeći od smrti. Bori se svim načinima pronaći formulu za vječnost i besmrtnost. U susretu sa smrću služimo se brojnim mehanizmima kojima se pokušavamo obraniti od negacije, identifikacije, introjekcije i drugog. (1) S obzirom da se zdravstveni djelatnici vrlo često susreću sa smrću, edukacija na temu suočavanja sa smrću iznimno je važna i neophodna kako bi olakšali prihvaćanje smrti umirućim pacijentima, članovima njihove obitelji, ali i kako bi osnažili i zaštitili sami sebe u suočavanju s takvim situacijama