AlphaFold2: A role for disordered protein prediction?

The development of AlphaFold2 was a paradigm-shift in the structural biology community; herein we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that a naive use of Dictionary of Secondary Structure of Proteins (DSSP) to separate ordered from disordered regions leads to a dramatic overestimation in disorder content, and that the Predicted Aligned Error (PAE) provides a much more rigorous metric. In addition, we show that even when used for disorder prediction, conventional predictors can outperform the PAE in disorder identification, and note an interesting relationship between the PAE and secondary structure that may explain our observations and hints at a broader application of the PAE to IDP dynamics.

flDPnn: Accurate intrinsic disorder prediction with putative propensities of disorder functions

Identification of intrinsic disorder in proteins relies in large part on computational predictors, which demands that their accuracy should be high. Since intrinsic disorder carries out a broad range of cellular functions, it is desirable to couple the disorder and disorder function predictions. We report a computational tool, flDPnn, that provides accurate, fast and comprehensive disorder and disorder function predictions from protein sequences. The recent Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment and results on other test datasets demonstrate that flDPnn offers accurate predictions of disorder, fully disordered proteins and four common disorder functions. These predictions are substantially better than the results of the existing disorder predictors and methods that predict functions of disorder. Ablation tests reveal that the high predictive performance stems from innovative ways used in flDPnn to derive sequence profiles and encode inputs. flDPnn’s webserver is available at http://biomine.cs.vcu.edu/servers/flDPnn/

metapredict: a fast, accurate, and easy-to-use cross-platform predictor of consensus disorder

Intrinsically disordered proteins and protein regions make up a substantial fraction of many proteomes where they play a wide variety of essential roles. A critical first step in understanding the role of disordered protein regions in biological function is to identify those disordered regions correctly. Computational methods for disorder prediction have emerged as a core set of tools to guide experiments, interpret results, and develop hypotheses. Given the multiple different predictors available, consensus scores have emerged as a popular approach to mitigate biases or limitations of any single method. Consensus scores integrate the outcome of multiple independent disorder predictors and provide a per-residue value that reflects the number of tools that predict a residue to be disordered. Although consensus scores help mitigate the inherent problems of using any single disorder predictor, they are computationally expensive to generate. They also necessitate the installation of multiple different software tools, which can be prohibitively difficult. To address this challenge, we developed a deep-learning-based predictor of consensus disorder scores. Our predictor, metapredict, utilizes a bidirectional recurrent neural network trained on the consensus disorder scores from 12 proteomes. By benchmarking metapredict using two orthogonal approaches, we found that metapredict is among the most accurate disorder predictors currently available. Metapredict is also remarkably fast, enabling proteome-scale disorder prediction in minutes. Metapredict is fully open source and is distributed as a Python package, a collection of command-line tools, and a web server. We believe metapredict offers a convenient, accessible, accurate, and high-performance predictor for single-proteins and proteomes alike.

Critical assessment of protein intrinsic disorder prediction

Intrinsically disordered proteins, defying the traditional protein structure–function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.

Machine learning for psychological disorder prediction in Indians during COVID-19 nationwide lockdown

As the world combats with the outrageous and perilous novel coronavirus, national lockdown has been enforced in most of the countries. It is necessary for public health but on the flip side it is detrimental for people’s mental health. While the psychological repercussions are predictable during the period of COVID-19 lockdown but this enforcement can lead to long-term behavioral changes post lockdown too. Moreover, the detection of psychological effects may take months or years. This mental health crisis situation requires timely, pro-active intervention to cope and persevere the Coro-anxiety (Corona-related). To address this gap, this research firstly studies the psychological burden among Indians using a COVID-19 Mental Health Questionnaire and then does a predictive analytics using machine learning to identify the likelihood of mental health outcomes using learned features of 395 Indian participants. The proposed Psychological Disorder Prediction (PDP) tool uses a multinomial Naïve Bayes classifier to train the model to detect the onset of specific psychological disorder and classify the participants into two pre-defined categories, namely, anxiety disorder and mood disorder. Experimental evaluation reports a classification accuracy of 92.15%. This automation plays a pivotal role in clinical support as it aims to suggest individuals who may need psychological help.