DTDHM: detection of tandem duplications based on hybrid methods using next-generation sequencing data.

Background: Tandem duplication (TD) is a common and important type of structural variation in the human genome. TDs have been shown to play an essential role in many diseases, including cancer. However, it is difficult to accurately detect TDs due to the uneven distribution of reads and the inherent complexity of next-generation sequencing (NGS) data. Methods: This article proposes a method called DTDHM (detection of tandem duplications based on hybrid methods), which utilizes NGS data to detect TDs in a single sample. DTDHM builds a pipeline that integrates read depth (RD), split read (SR), and paired-end mapping (PEM) signals. To solve the problem of uneven distribution of normal and abnormal samples, DTDHM uses the K-nearest neighbor (KNN) algorithm for multi-feature classification prediction. Then, the qualified split reads and discordant reads are extracted and analyzed to achieve accurate localization of variation sites. This article compares DTDHM with three other methods on 450 simulated datasets and five real datasets. Results: In 450 simulated data samples, DTDHM consistently maintained the highest F1-score. The average F1-score of DTDHM, SVIM, TARDIS, and TIDDIT were 80.0%, 56.2%, 43.4%, and 67.1%, respectively. The F1-score of DTDHM had a small variation range and its detection effect was the most stable and 1.2 times that of the suboptimal method. Most of the boundary biases of DTDHM fluctuated around 20 bp, and its boundary deviation detection ability was better than TARDIS and TIDDIT. In real data experiments, five real sequencing samples (NA19238, NA19239, NA19240, HG00266, and NA12891) were used to test DTDHM. The results showed that DTDHM had the highest overlap density score (ODS) and F1-score of the four methods. Conclusions: Compared with the other three methods, DTDHM achieved excellent results in terms of sensitivity, precision, F1-score, and boundary bias. These results indicate that DTDHM can be used as a reliable tool for detecting TDs from NGS data, especially in the case of low coverage depth and tumor purity samples.

Dietary patterns and the risk of diabetes in Korean adults: A cross-sectional and prospective cohort study.

OBJECTIVE: The aim of this study was to identify dietary patterns associated with diabetes in Korean adults and to investigate their association with diabetes risk in both a cross-sectional and prospective study. METHODS: Predefined food groups collected by the Korea National Health and Nutrition Examination Survey (KNHANES 2015-2018, n = 19 721) were entered in a reduced rank regression (RRR) model, followed by stepwise linear regression analyses to identify the most predictive dietary patterns. We evaluated the construct validity of dietary patterns in two independent samples from KNHANES 2019 to 2021 (n = 14 223) and the Health Examinees (HEXA) cohort study (n = 30 013). Associations between dietary patterns and diabetes risk were examined using multivariable regression and multivariable-adjusted Cox proportional hazard models, respectively. RESULTS: A dietary pattern was identified with high positive loadings for refined white rice, kimchi and salted vegetables, wheat flour and bread, and seasonings, and high negative loadings for whole grains, legumes with tofu and soymilk, poultry, eggs, and plant oils. The higher pattern scores were significantly associated with diabetes risk in KNHANES 2015 to 2018 (male: odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.35, 1.88; female: OR: 1.37; 95% CI: 1.18, 1.52), KNHANES 2019 to 2021 (male: OR: 1.47; 95% CI: 1.01, 1.69; female: OR: 1.37; 95% CI: 1.18, 1.54), and HEXA study (male: hazard ratio [HR]: 1.10; 95% CI: 1.01, 1.34; female: HR: 1.24; 95% CI: 1.02, 1.52). CONCLUSIONS: Dietary patterns derived by RRR followed by stepwise linear regression analyses were associated with increased risks of diabetes among Korean adults.

An interpretable online prediction method for remaining useful life of lithium-ion batteries.

Accurate prediction of the remaining useful life (RUL) of lithium-ion batteries is advantageous for maintaining the stability of electrical systems. In this paper, an interpretable online method which can reflect capacity regeneration is proposed to accurately estimate the RUL. Firstly, four health indicators (HIs) are extracted from the charging and discharging process for online prediction. Then, the HIs model is trained using support vector regression to obtain future features. And the capacity model of Gaussian process regression (GPR) is trained and analyzed by Shapley additive explanation (SHAP). Meanwhile, the state space for capacity prediction is constructed with the addition of Gaussian non-white noise to simulate the capacity regeneration. And the modified predicted HIs and noise are obtained by unscented Kalman filter. Finally, according to SHAP explainer, the predicted HIs acting as the baseline and the modified HIs containing information on capacity regeneration are chosen to predict RUL. In addition, the bounds of confidence intervals (CIs) are calculated separately to reflect the regenerated capacity. The experimental results demonstrate that the proposed online method can achieve high accuracy and effectively capture the capacity regeneration. The absolute error of failure RUL is below 5 and the minimum confidence interval is only 2.

An analysis of case studies for advancing photovoltaic power forecasting through multi-scale fusion techniques.

Integration renewable energy sources into current power generation systems necessitates accurate forecasting to optimize and preserve supply-demand restrictions in the electrical grids. Due to the highly random nature of environmental conditions, accurate prediction of PV power has limitations, particularly on long and short periods. Thus, this research provides a new hybrid model for forecasting short PV power based on the fusing of multi-frequency information of different decomposition techniques that will allow a forecaster to provide reliable forecasts. We evaluate and provide insights into the performance of five multi-scale decomposition algorithms combined with a deep convolution neural network (CNN). Additionally, we compare the suggested combination approach's performance to that of existing forecast models. An exhaustive assessment is carried out using three grid-connected PV power plants in Algeria with a total installed capacity of 73.1 MW. The developed fusing strategy displayed an outstanding forecasting performance. The comparative analysis of the proposed combination method with the stand-alone forecast model and other hybridization techniques proves its superiority in terms of forecasting precision, with an RMSE varying in the range of [0.454-1.54] for the three studied PV stations.

Corrigendum: The disease associated Tau35 fragment has an increased propensity to aggregate compared to full-length tau.

[This corrects the article DOI: 10.3389/fmolb.2021.779240.].

[Recanalization of colon in the treatment of patients with acute malignant obstructive colonic obstruction]. / Metody rekanalizatsii tolstoi kishki v lechenii bol'nykh ostroi obturatsionnoi tolstokishechnoi neprokhodimost'yu zlokachestvennogo geneza.

OBJECTIVE: To analyze available literature data on the methods of colon recanalization in patients with acute malignant obstructive colonic obstruction. MATERIAL AND METHODS: We retrospectively analyzed literature data on the treatment of acute neoplastic colonic obstruction. RESULTS: We reviewed available national and foreign literature data on various methods of colon recanalization including various modern and hybrid techniques. CONCLUSION: Methods of colon recanalization with subsequent stenting are the most optimal for preoperative decompression of colon. These measures are effective and allow postponing radical surgery or avoiding it altogether without worsening the prognosis of the underlying pathology. However, there is a small amount of literature data on modern hybrid methods of recanalization.

Effect of phosphorylation on the structural dynamics, thermal stability of human dopamine transporter: A simulation study using normal modes, molecular dynamics and Markov State Model.

The Human Dopamine Transporter (hDAT) plays an essential role in modulating the Influx/Efflux of dopamine, and it is involved in the mechanism of certain neurodegenerative diseases such as Parkinson's disease. Several studies have reported important states for Dopamine transport: outward-facing open state (OFo), the outward-facing closed state (OFc), the holo-occluded state closed (holo), and the inward-facing open state (IFo). Furthermore, experimental assays have shown that different phosphorylation conditions in hDAT can affect the rate of dopamine absorption. We present a protocol using hybrid simulation methods to study the conformational dynamics and stability of states of hDAT under different phosphorylation sites. With this protocol, we explored the conformational space of hDAT, identified the states, and evaluated the free energy differences and the transition probabilities between them in each of the phosphorylation cases. We also presented the conformational changes and correlated them with those described in the literature. There is a thesis/hypothesis that the phosphorylation condition corresponding to NP-333 system (where all sites Ser/Thr from residue 2 to 62 and 254 to 613 are phosphorylated, except residue 333) would decrease the rate of dopamine transport from the extracellular medium to the intracellular medium by hDAT as previously described in the literature by Lin et al., 2003. Our results corroborated this thesis/hypothesis and the data reported. It is probably due to the affectation/changes/alteration of the conformational dynamics of this system that makes the intermediate states more likely and makes it difficult to initial states associated with the uptake of dopamine in the extracellular medium, corroborating the experimental results. Furthermore, our results showed that just single phosphorylation/dephosphorylation could alter intrinsic protein motions affecting the sampling of one or more states necessary for dopamine transport. In this sense, the modification of phosphorylation influences protein movements and conformational preferences, affecting the stability of states and the transition between them and, therefore, the transport.

Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution, new validation tools, and implications for the future.

As a discipline, structural biology has been transformed by the three-dimensional electron microscopy (3DEM) "Resolution Revolution" made possible by convergence of robust cryo-preservation of vitrified biological materials, sample handling systems, and measurement stages operating a liquid nitrogen temperature, improvements in electron optics that preserve phase information at the atomic level, direct electron detectors (DEDs), high-speed computing with graphics processing units, and rapid advances in data acquisition and processing software. 3DEM structure information (atomic coordinates and related metadata) are archived in the open-access Protein Data Bank (PDB), which currently holds more than 11,000 3DEM structures of proteins and nucleic acids, and their complexes with one another and small-molecule ligands (~ 6% of the archive). Underlying experimental data (3DEM density maps and related metadata) are stored in the Electron Microscopy Data Bank (EMDB), which currently holds more than 21,000 3DEM density maps. After describing the history of the PDB and the Worldwide Protein Data Bank (wwPDB) partnership, which jointly manages both the PDB and EMDB archives, this review examines the origins of the resolution revolution and analyzes its impact on structural biology viewed through the lens of PDB holdings. Six areas of focus exemplifying the impact of 3DEM across the biosciences are discussed in detail (icosahedral viruses, ribosomes, integral membrane proteins, SARS-CoV-2 spike proteins, cryogenic electron tomography, and integrative structure determination combining 3DEM with complementary biophysical measurement techniques), followed by a review of 3DEM structure validation by the wwPDB that underscores the importance of community engagement.

Load Balancing Based on Firefly and Ant Colony Optimization Algorithms for Parallel Computing.

With the wide application of computational fluid dynamics in various fields and the continuous growth of the complexity of the problem and the scale of the computational grid, large-scale parallel computing came into being and became an indispensable means to solve this problem. In the numerical simulation of multi-block grids, the mapping strategy from grid block to processor is an important factor affecting the efficiency of load balancing and communication overhead. The multi-level graph partitioning algorithm is an important algorithm that introduces graph network dynamic programming to solve the load-balancing problem. This paper proposed a firefly-ant compound optimization (FaCO) algorithm for the weighted fusion of two optimization rules of the firefly and ant colony algorithm. For the graph, results after multi-level graph partitioning are transformed into a traveling salesman problem (TSP). This algorithm is used to optimize the load distribution of the solution, and finally, the rough graph segmentation is projected to obtain the most original segmentation optimization results. Although firefly algorithm (FA) and ant colony optimization (ACO), as swarm intelligence algorithms, are widely used to solve TSP problems, for the problems for which swarm intelligence algorithms easily fall into local optimization and low search accuracy, the improvement of the FaCO algorithm adjusts the weight of iterative location selection and updates the location. Experimental results on publicly available datasets such as the Oliver30 dataset and the eil51 dataset demonstrated the effectiveness of the FaCO algorithm. It is also significantly better than the commonly used firefly algorithm and other algorithms in terms of the search results and efficiency and achieves better results in optimizing the load-balancing problem of parallel computing.

Prototyping Crop Traits Retrieval Models for CHIME: Dimensionality Reduction Strategies Applied to PRISMA Data.

In preparation for new-generation imaging spectrometer missions and the accompanying unprecedented inflow of hyperspectral data, optimized models are needed to generate vegetation traits routinely. Hybrid models, combining radiative transfer models with machine learning algorithms, are preferred, however, dealing with spectral collinearity imposes an additional challenge. In this study, we analyzed two spectral dimensionality reduction methods: principal component analysis (PCA) and band ranking (BR), embedded in a hybrid workflow for the retrieval of specific leaf area (SLA), leaf area index (LAI), canopy water content (CWC), canopy chlorophyll content (CCC), the fraction of absorbed photosynthetic active radiation (FAPAR), and fractional vegetation cover (FVC). The SCOPE model was used to simulate training data sets, which were optimized with active learning. Gaussian process regression (GPR) algorithms were trained over the simulations to obtain trait-specific models. The inclusion of PCA and BR with 20 features led to the so-called GPR-20PCA and GPR-20BR models. The 20PCA models encompassed over 99.95% cumulative variance of the full spectral data, while the GPR-20BR models were based on the 20 most sensitive bands. Validation against in situ data obtained moderate to optimal results with normalized root mean squared error (NRMSE) from 13.9% (CWC) to 22.3% (CCC) for GPR-20PCA models, and NRMSE from 19.6% (CWC) to 29.1% (SLA) for GPR-20BR models. Overall, the GPR-20PCA slightly outperformed the GPR-20BR models for all six variables. To demonstrate mapping capabilities, both models were tested on a PRecursore IperSpettrale della Missione Applicativa (PRISMA) scene, spectrally resampled to Copernicus Hyperspectral Imaging Mission for the Environment (CHIME), over an agricultural test site (Jolanda di Savoia, Italy). The two strategies obtained plausible spatial patterns, and consistency between the two models was highest for FVC and LAI (R 2 = 0.91, R 2 = 0.86) and lowest for SLA mapping (R 2 = 0.53). From these findings, we recommend implementing GPR-20PCA models as the most efficient strategy for the retrieval of multiple crop traits from hyperspectral data streams. Hence, this workflow will support and facilitate the preparations of traits retrieval models from the next-generation operational CHIME.

A Hybrid Structural Method for Investigating Low Molecular Weight Oligomeric Structures of Amyloid Beta.

Spurred in part by the failure of recent therapeutics targeting amyloid ß plaques in Alzheimer's Disease (AD), attention is increasingly turning to the oligomeric forms of this peptide that form early in the aggregation process. However, while numerous amyloid ß fibril structures have been characterized, primarily by NMR spectroscopy and cryo-EM, obtaining structural information on the low molecular weight forms of amyloid ß that presumably precede and/or seed fibril formation has proved challenging. These transient forms are heterogeneous, and depend heavily on experimental conditions such as buffer, temperature, concentration, and degree of quiescence during measurement. Here, we present the concept for a new approach to delineating structural features of early-stage low molecular weight amyloid ß oligomers, using a solvent accessibility assay in conjunction with simultaneous fluorescence measurements.

Hybrid Methods of Bibliographic Coupling and Text Similarity Measurement for Biomedical Paper Recommendation.

The amount of available scientific literature is increasing, and studies have proposed various methods for evaluating document-document similarity in order to cluster or classify documents for science mapping and knowledge discovery. In this paper, we propose hybrid methods for bibliographic coupling (BC) and linear evaluation of text or content similarity: We combined BC with BM25, Cosine, and PMRA to compare their performances with single methods in paper recommendation tasks using TREC Genomics Track 2005datasets. For paper recommendation, BC and text-based methods complement each other, and hybrid methods were better than single methods. The combinations of BC with BM25 and BC with Cosine performed better than BC with PMRA. The performances were best when the weights of BM25, Cosine, and PMRA were 0.025, 0.2, and 0.2, respectively, in hybrid methods. For paper recommendation, the combinations of BC with text-based methods were better than BC or text-based methods used alone. The choice of method should depend on the actual data and research needs. In the future, the underlying reasons for the differences in performance and the specific part or type of information they complement in text clustering or recommendation need to be examined.

Associations between dietary patterns and cardiovascular disease risk in Canadian adults: a comparison of partial least squares, reduced rank regression, and the simplified dietary pattern technique.

BACKGROUND: Hybrid methodologies have gained continuing interest as unique data reduction techniques for establishing a direct link between dietary exposures and clinical outcomes. OBJECTIVES: We aimed to compare partial least squares (PLS) and reduced rank regression (RRR) in identifying a dietary pattern associated with a high cardiovascular disease (CVD) risk in Canadian adults, construct PLS- and RRR-based simplified dietary patterns, and assess associations between the 4 dietary pattern scores and CVD risk. METHODS: Data were collected from 24-h dietary recalls of adult respondents in the 2 cycles of the nationally representative Canadian Community Health Survey (CCHS)-Nutrition: CCHS 2004 linked to health administrative databases (n = 12,313) and CCHS 2015 (n = 14,020). Using 39 food groups, PLS and RRR were applied for identification of an energy-dense (ED), high-saturated-fat (HSF), and low-fiber-density (LFD) dietary pattern. Associations of the derived dietary pattern scores with lifestyle characteristics and CVD risk were examined using weighted multivariate regression and weighted multivariable-adjusted Cox proportional hazard models, respectively. RESULTS: PLS and RRR identified highly similar ED, HSF, and LFD dietary patterns with common high positive loadings for fast food, carbonated drinks, salty snacks, and solid fats, and high negative loadings for fruit, dark green vegetables, red and orange vegetables, other vegetables, whole grains, and legumes and soy (≥|0.17|). Food groups with the highest loadings were summed to form simplified pattern scores. Although the dietary patterns were not significantly associated with CVD risk, they were positively associated with 402-kcal/d higher energy intake (P-trends < 0.05) and higher obesity risk (PLS: OR: 2.09; 95% CI: 1.62, 2.70; RRR: OR: 1.76; 95% CI: 1.44, 2.17) (P-trends < 0.0001) in the fourth quartiles. CONCLUSIONS: PLS and RRR were shown to be equally effective for the derivation of a high-CVD-risk dietary pattern among Canadian adults. Further research is warranted on the role of major dietary components in cardiovascular health.

Protein structure prediction using residue-resolved protection factors from hydrogen-deuterium exchange NMR.

Hydrogen-deuterium exchange (HDX) measured by nuclear magnetic resonance (NMR) provides structural information for proteins relating to solvent accessibility and flexibility. While this structural information is beneficial, the data cannot be used exclusively to elucidate structures. However, the structural information provided by the HDX-NMR data can be supplemented by computational methods. In previous work, we developed an algorithm in Rosetta to predict structures using qualitative HDX-NMR data (categories of exchange rate). Here we expand on the effort, and utilize quantitative protection factors (PFs) from HDX-NMR for structure prediction. From observed correlations between PFs and solvent accessibility/flexibility measures, we present a scoring function to quantify the agreement with HDX data. Using a benchmark set of 10 proteins, an average improvement of 5.13 Å in root-mean-square deviation (RMSD) is observed for cases of inaccurate Rosetta predictions. Ultimately, seven out of 10 predictions are accurate without including HDX data, and nine out of 10 are accurate when using our PF-based HDX score.

The Disease Associated Tau35 Fragment has an Increased Propensity to Aggregate Compared to Full-Length Tau.

Tau35 is a truncated form of tau found in human brain in a subset of tauopathies. Tau35 expression in mice recapitulates key features of human disease, including progressive increase in tau phosphorylation, along with cognitive and motor dysfunction. The appearance of aggregated tau suggests that Tau35 may have structural properties distinct from those of other tau species that could account for its pathological role in disease. To address this hypothesis, we performed a structural characterization of monomeric and aggregated Tau35 and compared the results to those of two longer isoforms, 2N3R and 2N4R tau. We used small angle X-ray scattering to show that Tau35, 2N3R and 2N4R tau all behave as disordered monomeric species but Tau35 exhibits higher rigidity. In the presence of the poly-anion heparin, Tau35 increases thioflavin T fluorescence significantly faster and to a greater extent than full-length tau, demonstrating a higher propensity to aggregate. By using atomic force microscopy, circular dichroism, transmission electron microscopy and X-ray fiber diffraction, we provide evidence that Tau35 aggregation is mechanistically and morphologically similar to previously reported tau fibrils but they are more densely packed. These data increase our understanding of the aggregation inducing properties of clinically relevant tau fragments and their potentially damaging role in the pathogenesis of human tauopathies.

Improving the performance of deep learning models using statistical features: The case study of COVID-19 forecasting.

COVID-19 pandemic has affected all aspects of people's lives and disrupted the economy. Forecasting the number of cases infected with this virus can help authorities make accurate decisions on the interventions that must be implemented to control the pandemic. Investigation of the studies on COVID-19 forecasting indicates that various techniques such as statistical, mathematical, and machine and deep learning have been utilized. Although deep learning models have shown promising results in this context, their performance can be improved using auxiliary features. Therefore, in this study, we propose two hybrid deep learning methods that utilize the statistical features as auxiliary inputs and associate them with their main input. Specifically, we design a hybrid method of the multihead attention mechanism and the statistical features (ATT_FE) and a combined method of convolutional neural network and the statistical features (CNN_FE) and apply them to COVID-19 data of 10 countries with the highest number of confirmed cases. The results of experiments indicate that the hybrid models outperform their conventional counterparts in terms of performance measures. The experiments also demonstrate the superiority of the hybrid ATT_FE method over the long short-term memory model.

The Protein Data Bank Archive.

Protein Data Bank is the single worldwide archive of experimentally determined macromolecular structure data. Established in 1971 as the first open access data resource in biology, the PDB archive is managed by the worldwide Protein Data Bank (wwPDB) consortium which has four partners-the RCSB Protein Data Bank (RCSB PDB; rcsb.org), the Protein Data Bank Japan (PDBj; pdbj.org), the Protein Data Bank in Europe (PDBe; pdbe.org), and BioMagResBank (BMRB; www.bmrb.wisc.edu ). The PDB archive currently includes ~175,000 entries. The wwPDB has established a number of task forces and working groups that bring together experts form the community who provide recommendations on improving data standards and data validation for improving data quality and integrity. The wwPDB members continue to develop the joint deposition, biocuration, and validation system (OneDep) to improve data quality and accommodate new data from emerging techniques such as 3DEM. Each PDB entry contains coordinate model and associated metadata for all experimentally determined atomic structures, experimental data for the traditional structure determination techniques (X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy), validation reports, and additional information on quaternary structures. The wwPDB partners are committed to following the FAIR (Findability, Accessibility, Interoperability, and Reproducibility) principles and have implemented a DOI resolution mechanism that provides access to all the relevant files for a given PDB entry. On average, >250 new entries are added to the archive every week and made available by each wwPDB partner via FTP area. The wwPDB partner sites also develop data access and analysis tools and make these available via their websites. wwPDB continues to work with experts in the community to establish a federation of archives for archiving structures determined using integrative/hybrid method where multiple experimental techniques are used.

Incorporating domain growth into hybrid methods for reaction-diffusion systems.

Reaction-diffusion mechanisms are a robust paradigm that can be used to represent many biological and physical phenomena over multiple spatial scales. Applications include intracellular dynamics, the migration of cells and the patterns formed by vegetation in semi-arid landscapes. Moreover, domain growth is an important process for embryonic growth and wound healing. There are many numerical modelling frameworks capable of simulating such systems on growing domains; however, each of these may be well suited to different spatial scales and particle numbers. Recently, spatially extended hybrid methods on static domains have been produced to bridge the gap between these different modelling paradigms in order to represent multi-scale phenomena. However, such methods have not been developed with domain growth in mind. In this paper, we develop three hybrid methods on growing domains, extending three of the prominent static-domain hybrid methods. We also provide detailed algorithms to allow others to employ them. We demonstrate that the methods are able to accurately model three representative reaction-diffusion systems accurately and without bias.

Flood susceptibility mapping by integrating frequency ratio and index of entropy with multilayer perceptron and classification and regression tree.

Episodes of frequent flooding continue to increase, often causing serious damage and tools to identify areas affected by such disasters have become indispensable in today's society. Using the latest techniques can make very accurate flood predictions. In this study, we introduce four effective methods to evaluate the flood susceptibility of Poyang County, in China, by integrating two independent models of frequency ratio and index of entropy with multilayer perceptron and classification and regression tree models. The flood locations of the study area were identified through the flood inventory process, and 12 flood conditioning factors were used in the training and validation processes. According to the results of the linear support vector machine, elevation, slope angle, and soil have the highest predictive ability. The experimental results of the four hybrid models demonstrate that between 20% and 50% of the study area has high and very high flood susceptibility. The multilayer perceptron-probability density hybrid model is the most effective among the six comparative methods.

Capturing the Conformational Ensemble of the Mixed Folded Polyglutamine Protein Ataxin-3.

Ataxin-3 is a deubiquitinase involved in protein quality control and other essential cellular functions. It preferentially interacts with polyubiquitin chains of four or more units attached to proteins delivered to the ubiquitin-proteasome system. Ataxin-3 is composed of an N-terminal Josephin domain and a flexible C terminus that contains two or three ubiquitin-interacting motifs (UIMs) and a polyglutamine tract, which, when expanded beyond a threshold, leads to protein aggregation and misfolding and causes spinocerebellar ataxia type 3. The high-resolution structure of the Josephin domain is available, but the structural and dynamical heterogeneity of ataxin-3 has so far hindered the structural description of the full-length protein. Here, we characterize non-expanded and expanded variants of ataxin-3 in terms of conformational ensembles adopted by the proteins in solution by jointly using experimental data from nuclear magnetic resonance and small-angle X-ray scattering with coarse-grained simulations. Our results pave the way to a molecular understanding of polyubiquitin recognition.