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Jonas Adler

Bio: Jonas Adler is an academic researcher from Royal Institute of Technology. The author has contributed to research in topics: Inverse problem & Iterative reconstruction. The author has an hindex of 14, co-authored 34 publications receiving 2551 citations.

Papers
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Journal ArticleDOI
15 Jul 2021-Nature
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
Abstract: Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort1–4, the structures of around 100,000 unique proteins have been determined5, but this represents a small fraction of the billions of known protein sequences6,7. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’8—has been an important open research problem for more than 50 years9. Despite recent progress10–14, existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14)15, demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

10,601 citations

Journal ArticleDOI
22 Jul 2021-Nature
TL;DR: The AlphaFold2 dataset as discussed by the authors is a large-scale and high-accuracy structure prediction dataset for protein structures, which is used to evaluate the structural properties of proteins.
Abstract: Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally-determined structure1. Here we dramatically expand structural coverage by applying the state-of-the-art machine learning method, AlphaFold2, at scale to almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model, and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions likely to be disordered. Finally, we provide some case studies illustrating how high-quality predictions may be used to generate biological hypotheses. Importantly, we are making our predictions freely available to the community via a public database (hosted by the European Bioinformatics Institute at https://alphafold.ebi.ac.uk/ ). We anticipate that routine large-scale and high-accuracy structure prediction will become an important tool, allowing new questions to be addressed from a structural perspective.

1,238 citations

Journal ArticleDOI
TL;DR: The Learned Primal-Dual algorithm for tomographic reconstruction accounts for a (possibly non-linear) forward operator in a deep neural network by unrolling a proximal primal-dual optimization method, but where the proximal operators have been replaced with convolutional neural networks.
Abstract: We propose the Learned Primal-Dual algorithm for tomographic reconstruction. The algorithm accounts for a (possibly non-linear) forward operator in a deep neural network by unrolling a proximal primal-dual optimization method, but where the proximal operators have been replaced with convolutional neural networks. The algorithm is trained end-to-end, working directly from raw measured data and it does not depend on any initial reconstruction such as filtered back-projection (FBP). We compare performance of the proposed method on low dose computed tomography reconstruction against FBP, total variation (TV), and deep learning based post-processing of FBP. For the Shepp-Logan phantom we obtain >6 dB peak signal to noise ratio improvement against all compared methods. For human phantoms the corresponding improvement is 6.6 dB over TV and 2.2 dB over learned post-processing along with a substantial improvement in the structural similarity index. Finally, our algorithm involves only ten forward-back-projection computations, making the method feasible for time critical clinical applications.

556 citations

Journal ArticleDOI
TL;DR: In this article, a partially learned approach for the solution of ill-posed inverse problems with not necessarily linear forward operators is proposed, which builds on ideas from classical regularisation theory.
Abstract: We propose a partially learned approach for the solution of ill-posed inverse problems with not necessarily linear forward operators. The method builds on ideas from classical regularisation theory ...

517 citations

Journal ArticleDOI
TL;DR: In this article, the learned primal-dual (LPD) algorithm is proposed for tomographic reconstruction, where the proximal operators have been replaced with convolutional neural networks and the algorithm is trained end-to-end, working directly from raw measured data.
Abstract: We propose the Learned Primal-Dual algorithm for tomographic reconstruction. The algorithm accounts for a (possibly non-linear) forward operator in a deep neural network by unrolling a proximal primal-dual optimization method, but where the proximal operators have been replaced with convolutional neural networks. The algorithm is trained end-to-end, working directly from raw measured data and it does not depend on any initial reconstruction such as FBP. We compare performance of the proposed method on low dose CT reconstruction against FBP, TV, and deep learning based post-processing of FBP. For the Shepp-Logan phantom we obtain >6dB PSNR improvement against all compared methods. For human phantoms the corresponding improvement is 6.6dB over TV and 2.2dB over learned post-processing along with a substantial improvement in the SSIM. Finally, our algorithm involves only ten forward-back-projection computations, making the method feasible for time critical clinical applications.

403 citations


Cited by
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Journal ArticleDOI
15 Jul 2021-Nature
TL;DR: For example, AlphaFold as mentioned in this paper predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture. But the accuracy is limited by the fact that no homologous structure is available.
Abstract: Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort1–4, the structures of around 100,000 unique proteins have been determined5, but this represents a small fraction of the billions of known protein sequences6,7. Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’8—has been an important open research problem for more than 50 years9. Despite recent progress10–14, existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14)15, demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

10,601 citations

01 Jan 2004
TL;DR: Comprehensive and up-to-date, this book includes essential topics that either reflect practical significance or are of theoretical importance and describes numerous important application areas such as image based rendering and digital libraries.
Abstract: From the Publisher: The accessible presentation of this book gives both a general view of the entire computer vision enterprise and also offers sufficient detail to be able to build useful applications. Users learn techniques that have proven to be useful by first-hand experience and a wide range of mathematical methods. A CD-ROM with every copy of the text contains source code for programming practice, color images, and illustrative movies. Comprehensive and up-to-date, this book includes essential topics that either reflect practical significance or are of theoretical importance. Topics are discussed in substantial and increasing depth. Application surveys describe numerous important application areas such as image based rendering and digital libraries. Many important algorithms broken down and illustrated in pseudo code. Appropriate for use by engineers as a comprehensive reference to the computer vision enterprise.

3,627 citations

Journal ArticleDOI
TL;DR: The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure predictions.
Abstract: The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure predictions. Powered by AlphaFold v2.0 of DeepMind, it has enabled an unprecedented expansion of the structural coverage of the known protein-sequence space. AlphaFold DB provides programmatic access to and interactive visualization of predicted atomic coordinates, per-residue and pairwise model-confidence estimates and predicted aligned errors. The initial release of AlphaFold DB contains over 360,000 predicted structures across 21 model-organism proteomes, which will soon be expanded to cover most of the (over 100 million) representative sequences from the UniRef90 data set.

2,008 citations

Journal ArticleDOI
TL;DR: ColabFold as discussed by the authors combines the fast homology search of MMseqs2 with AlphaFold2 or RoseTTAFold for protein folding and achieves 40-60fold faster search and optimized model utilization.
Abstract: ColabFold offers accelerated prediction of protein structures and complexes by combining the fast homology search of MMseqs2 with AlphaFold2 or RoseTTAFold. ColabFold's 40-60-fold faster search and optimized model utilization enables prediction of close to 1,000 structures per day on a server with one graphics processing unit. Coupled with Google Colaboratory, ColabFold becomes a free and accessible platform for protein folding. ColabFold is open-source software available at https://github.com/sokrypton/ColabFold and its novel environmental databases are available at https://colabfold.mmseqs.com .

1,553 citations