CRFalign: A Sequence-Structure Alignment of Proteins Based on a Combination of HMM-HMM Comparison and Conditional Random Fields.

Sequence-structure alignment for protein sequences is an important task for the template-based modeling of 3D structures of proteins. Building a reliable sequence-structure alignment is a challenging problem, especially for remote homologue target proteins. We built a method of sequence-structure alignment called CRFalign, which improves upon a base alignment model based on HMM-HMM comparison by employing pairwise conditional random fields in combination with nonlinear scoring functions of structural and sequence features. Nonlinear scoring part is implemented by a set of gradient boosted regression trees. In addition to sequence profile features, various position-dependent structural features are employed including secondary structures and solvent accessibilities. Training is performed on reference alignments at superfamily levels or twilight zone chosen from the SABmark benchmark set. We found that CRFalign method produces relative improvement in terms of average alignment accuracies for validation sets of SABmark benchmark. We also tested CRFalign on 51 sequence-structure pairs involving 15 FM target domains of CASP14, where we could see that CRFalign leads to an improvement in average modeling accuracies in these hard targets (TM-CRFalign ≃42.94%) compared with that of HHalign (TM-HHalign ≃39.05%) and also that of MRFalign (TM-MRFalign ≃36.93%). CRFalign was incorporated to our template search framework called CRFpred and was tested for a random target set of 300 target proteins consisting of Easy, Medium and Hard sets which showed a reasonable template search performance.

Protein structure modeling for CASP10 by multiple layers of global optimization.

In the template-based modeling (TBM) category of CASP10 experiment, we introduced a new protocol called protein modeling system (PMS) to generate accurate protein structures in terms of side-chains as well as backbone trace. In the new protocol, a global optimization algorithm, called conformational space annealing (CSA), is applied to the three layers of TBM procedure: multiple sequence-structure alignment, 3D chain building, and side-chain re-modeling. For 3D chain building, we developed a new energy function which includes new distance restraint terms of Lorentzian type (derived from multiple templates), and new energy terms that combine (physical) energy terms such as dynamic fragment assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term, etc. These physical energy terms are expected to guide the structure modeling especially for loop regions where no template structures are available. In addition, we developed a new quality assessment method based on random forest machine learning algorithm to screen templates, multiple alignments, and final models. For TBM targets of CASP10, we find that, due to the combination of three stages of CSA global optimizations and quality assessment, the modeling accuracy of PMS improves at each additional stage of the protocol. It is especially noteworthy that the side-chains of the final PMS models are far more accurate than the models in the intermediate steps.

Improved Correction of Atmospheric Pressure Data Obtained by Smartphones through Machine Learning.

A correction method using machine learning aims to improve the conventional linear regression (LR) based method for correction of atmospheric pressure data obtained by smartphones. The method proposed in this study conducts clustering and regression analysis with time domain classification. Data obtained in Gyeonggi-do, one of the most populous provinces in South Korea surrounding Seoul with the size of 10,000 km(2), from July 2014 through December 2014, using smartphones were classified with respect to time of day (daytime or nighttime) as well as day of the week (weekday or weekend) and the user's mobility, prior to the expectation-maximization (EM) clustering. Subsequently, the results were analyzed for comparison by applying machine learning methods such as multilayer perceptron (MLP) and support vector regression (SVR). The results showed a mean absolute error (MAE) 26% lower on average when regression analysis was performed through EM clustering compared to that obtained without EM clustering. For machine learning methods, the MAE for SVR was around 31% lower for LR and about 19% lower for MLP. It is concluded that pressure data from smartphones are as good as the ones from national automatic weather station (AWS) network.