Accuracy of structure-based sequence alignment of automatic methods

<p>Abstract</p> <p>Background</p> <p>Accurate sequence alignments are essential for homology searches and for building three-dimensional structural models of proteins. Since structure is better conserved than sequence, structure alignments have been used to guide sequence alignments and are commonly used as the gold standard for sequence alignment evaluation. Nonetheless, as far as we know, there is no report of a systematic evaluation of pairwise structure alignment programs in terms of the sequence alignment accuracy.</p> <p>Results</p> <p>In this study, we evaluate CE, DaliLite, FAST, LOCK2, MATRAS, SHEBA and VAST in terms of the accuracy of the sequence alignments they produce, using sequence alignments from NCBI's human-curated Conserved Domain Database (CDD) as the standard of truth. We find that 4 to 9% of the residues on average are either not aligned or aligned with more than 8 residues of shift error and that an additional 6 to 14% of residues on average are misaligned by 1–8 residues, depending on the program and the data set used. The fraction of correctly aligned residues generally decreases as the sequence similarity decreases or as the RMSD between the C_{<it>α </it>}positions of the two structures increases. It varies significantly across CDD superfamilies whether shift error is allowed or not. Also, alignments with different shift errors occur between proteins within the same CDD superfamily, leading to inconsistent alignments between superfamily members. In general, residue pairs that are more than 3.0 Å apart in the reference alignment are heavily (>= 25% on average) misaligned in the test alignments. In addition, each method shows a different pattern of relative weaknesses for different SCOP classes. CE gives relatively poor results for <it>β</it>-sheet-containing structures (all-<it>β</it>, <it>α</it>/<it>β</it>, and <it>α</it>+<it>β </it>classes), DaliLite for "others" class where all but the major four classes are combined, and LOCK2 and VAST for all-<it>β </it>and "others" classes.</p> <p>Conclusion</p> <p>When the sequence similarity is low, structure-based methods produce better sequence alignments than by using sequence similarities alone. However, current structure-based methods still mis-align 11–19% of the conserved core residues when compared to the human-curated CDD alignments. The alignment quality of each program depends on the protein structural type and similarity, with DaliLite showing the most agreement with CDD on average.</p

Deep reinforcement learning for large-eddy simulation modeling in wall-bounded turbulence

The development of a reliable subgrid-scale (SGS) model for large-eddy simulation (LES) is of great importance for many scientific and engineering applications. Recently, deep learning approaches have been tested for this purpose using high-fidelity data such as direct numerical simulation (DNS) in a supervised learning process. However, such data are generally not available in practice. Deep reinforcement learning (DRL) using only limited target statistics can be an alternative algorithm in which the training and testing of the model are conducted in the same LES environment. The DRL of turbulence modeling remains challenging owing to its chaotic nature, high dimensionality of the action space, and large computational cost. In the present study, we propose a physics-constrained DRL framework that can develop a deep neural network (DNN)-based SGS model for the LES of turbulent channel flow. The DRL models that produce the SGS stress were trained based on the local gradient of the filtered velocities. The developed SGS model automatically satisfies the reflectional invariance and wall boundary conditions without an extra training process so that DRL can quickly find the optimal policy. Furthermore, direct accumulation of reward, spatially and temporally correlated exploration, and the pre-training process are applied for the efficient and effective learning. In various environments, our DRL could discover SGS models that produce the viscous and Reynolds stress statistics perfectly consistent with the filtered DNS. By comparing various statistics obtained by the trained models and conventional SGS models, we present a possible interpretation of better performance of the DRL model

Iterative refinement of structure-based sequence alignments by Seed Extension

BACKGROUND: Accurate sequence alignment is required in many bioinformatics applications but, when sequence similarity is low, it is difficult to obtain accurate alignments based on sequence similarity alone. The accuracy improves when the structures are available, but current structure-based sequence alignment procedures still mis-align substantial numbers of residues. In order to correct such errors, we previously explored the possibility of replacing the residue-based dynamic programming algorithm in structure alignment procedures with the Seed Extension algorithm, which does not use a gap penalty. Here, we describe a new procedure called RSE (Refinement with Seed Extension) that iteratively refines a structure-based sequence alignment. RESULTS: RSE uses SE (Seed Extension) in its core, which is an algorithm that we reported recently for obtaining a sequence alignment from two superimposed structures. The RSE procedure was evaluated by comparing the correctly aligned fractions of residues before and after the refinement of the structure-based sequence alignments produced by popular programs. CE, DaliLite, FAST, LOCK2, MATRAS, MATT, TM-align, SHEBA and VAST were included in this analysis and the NCBI's CDD root node set was used as the reference alignments. RSE improved the average accuracy of sequence alignments for all programs tested when no shift error was allowed. The amount of improvement varied depending on the program. The average improvements were small for DaliLite and MATRAS but about 5% for CE and VAST. More substantial improvements have been seen in many individual cases. The additional computation times required for the refinements were negligible compared to the times taken by the structure alignment programs. CONCLUSION: RSE is a computationally inexpensive way of improving the accuracy of a structure-based sequence alignment. It can be used as a standalone procedure following a regular structure-based sequence alignment or to replace the traditional iterative refinement procedures based on residue-level dynamic programming algorithm in many structure alignment programs

Neural networks for active drag reduction in fully turbulent airflows

This paper presents the application of a neural network controller to the problem of active drag reduction in a fully turbulent 3D fluid flow regime. Based on a successful yet infeasible previous active control scheme, we trained a neural network to mimic the control law using only surface spanwise shear stress measurements. We then demonstrate the ability of a neural controller implemented in an adaptive inverse model scheme to maintain a drag-reduced flow in a fully turbulent fluid simulation. By observing the weights of the on-line controller, a simple control law that predicts actuations proportional to the spanwise derivative of the spanwise shear stress is derived. Finally we examine the amount of parameter variation that may be required for a physical implementation of linear and nonlinear neural controllers

Attributing Image Generative Models using Latent Fingerprints

Generative models have enabled the creation of contents that are indistinguishable from those taken from the nature. Open-source development of such models raised concerns about the risks in their misuse for malicious purposes. One potential risk mitigation strategy is to attribute generative models via fingerprinting. Current fingerprinting methods exhibit significant tradeoff between robust attribution accuracy and generation quality, and also lack designing principles to improve this tradeoff. This paper investigates the use of latent semantic dimensions as fingerprints, from where we can analyze the effects of design variables, including the choice of fingerprinting dimensions, strength, and capacity, on the accuracy-quality tradeoff. Compared with previous SOTA, our method requires minimum computation and is more applicable to large-scale models. We use StyleGAN2 and the latent diffusion model to demonstrate the efficacy of our method