MRFalign: Protein Homology Detection through Alignment of Markov Random Fields

Sequence-based protein homology detection has been extensively studied and so far the most sensitive method is based upon comparison of protein sequence profiles, which are derived from multiple sequence alignment (MSA) of sequence homologs in a protein family. A sequence profile is usually represented as a position-specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and accordingly PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This paper presents a new homology detection method MRFalign, consisting of three key components: 1) a Markov Random Fields (MRF) representation of a protein family; 2) a scoring function measuring similarity of two MRFs; and 3) an efficient ADMM (Alternating Direction Method of Multipliers) algorithm aligning two MRFs. Compared to HMM that can only model very short-range residue correlation, MRFs can model long-range residue interaction pattern and thus, encode information for the global 3D structure of a protein family. Consequently, MRF-MRF comparison for remote homology detection shall be much more sensitive than HMM-HMM or PSSM-PSSM comparison. Experiments confirm that MRFalign outperforms several popular HMM or PSSM-based methods in terms of both alignment accuracy and remote homology detection and that MRFalign works particularly well for mainly beta proteins. For example, tested on the benchmark SCOP40 (8353 proteins) for homology detection, PSSM-PSSM and HMM-HMM succeed on 48% and 52% of proteins, respectively, at superfamily level, and on 15% and 27% of proteins, respectively, at fold level. In contrast, MRFalign succeeds on 57.3% and 42.5% of proteins at superfamily and fold level, respectively. This study implies that long-range residue interaction patterns are very helpful for sequence-based homology detection. The software is available for download at http://raptorx.uchicago.edu/download/.Comment: Accepted by both RECOMB 2014 and PLOS Computational Biolog

Instabilities of an eastern boundary current with and without large-scale flow influence

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution June 2011Eastern oceanic boundary currents are subject to hydrodynamic instability, generate small scale features that are visible in satellite images and may radiate westward into the interior, where they can be modified by the large-scale circulations. This thesis studies the stability of an eastern boundary current with and without the large-scale flow influence in an idealized framework represented by barotropic quasi-geostrophic dynamics. The linear stability analysis of a meridional current with a continuous velocity profile shows that meridional eastern and western boundary currents support a limited number of radiating modes with long meridional and zonal wavelengths and small growth rates. However, the linearly stable, long radiating modes of an eastern boundary current can become nonlinearly unstable by resonating with short trapped unstable modes. This phenomenon is clearly demonstrated in the weakly nonlinear simulations. Results suggest that linearly stable longwave modes deserve more attention when the radiating instability of a meridional boundary current is considered. A large-scale flow affects the short trapped unstable mode and long radiating mode through different mechanisms. The large-scale flow modifies the structure of the boundary current to stabilize or destabilize the unstable modes, leading to a meridionally localized maximum in the perturbation kinetic energy field. The shortwave mode is accelerated or decelerated by the meridional velocity adjustment of the large-scale flow to have an elongated or a squeezed meridional structure, which is confirmed both in a linear WKB analysis and in nonlinear simulations. The squeezed or elongated unstable mode detunes the nonlinear resonance with the longwave modes, which then become less energetic. These two modes show different meridional structures in kinetic energy field because of the different mechanisms. In spite of the model simplicity, these results can potentially explain the formation of the zonal jets observed in altimeter data, and indicate the influence of the large-scale wind-driven circulation on eastern boundary upwelling systems in the real ocean. Studies with more realistic configurations remain future challenges

On the warm bias along the South-West African Coast in coupled models : an oceanic perspective

Submitted in partial fulfillment of the requirements for the degree of Master of Science at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2008Coupled ocean/atmosphere simulations exhibit systematicwarm biases over the SouthWest African (SWA) coastal region. Recent investigations indicate that coastal ocean dynamics may play an important role in determining the SST patterns, but none of them provide a detailed analysis. In this study, I analyze simulations produced both by coupled models and by idealized models. Then results are interpreted on the basis of a theoretical framework. Finally the conclusion is reached that the insufficient resolution of the ocean component in the coupled model is responsible for the warm biases over the SWA coastal region. The coarse resolution used in the ocean model has an artificially stretched coastal side-wall boundary layer, which induces a smaller upwelling velocity in the boundary layer. The vertical heat transport decreases even when the volume transport is unchanged because of its nonlinear relationship with the magnitude of the upwelling velocity. Based on the scaling of the idealized model simulations, a simplified calculation shows that the vertical heat transport is inversely proportional to the zonal resolution over the coastal region. Therefore, increasing the horizontal resolution can considerably improve the coastal SST simulation, and better resolve the coastal dynamics