Reducing Dimensionality in Remote Homology Detection

Homology detection plays a major role in bioinformatics. Different type of methods is used for Homology detection. Here we extract the information from protein sequences and then uses the various algorithm to predict the similarity between protein families. SVM most commonly used the algorithm in homology detection. Classification techniques are not suitable for homology detection because theyare not suitable for high dimensional datasets. Soreducing the higher dimensionality is very important than easily can predict the similarity of protein families. Keywords: Homology detection, Protein, Sequence, Reducing dimensionality, BLAST, SCOP.

Transfer of Knowledge from Model Organisms to Evolutionarily Distant Non-Model Organisms: The Coral Pocillopora damicornis Membrane Signaling Receptome

With the ease of gene sequencing and the technology available to study and manipulate non-model organisms, the need to translate our understanding of model organisms to non-model organisms has become an urgent problem. For example, mining of large coral and their symbiont sequence data is a challenge, but also provides an opportunity for understanding functionality and evolution of these and other non-model organisms. Much more information than for any other eukaryotic species is available for humans, especially related to signal transduction and diseases. However, the coral cnidarian host and human have diverged over 700 million years ago and homologies between proteins are therefore often in the gray zone or undetectable with traditional BLAST searches. We introduce a two-stage approach to identifying putative coral homologues of human proteins. First, through remote homology detection using Hidden Markov Models, we identify candidate human homologues in the cnidarian genome. However, for many proteins, the human genome alone contains multiple family members with similar or even more divergence in sequence. In the second stage, therefore, we filter the remote homology results based on the functional and structural plausibility of each coral candidate, shortlisting the coral proteins likely to be true human homologues. We demonstrate our approach with a pipeline for mapping membrane receptors in humans to membrane receptors in corals, with specific focus on the stony coral, P. damicornis. More than 1000 human membrane receptors mapped to 335 coral receptors, including 151 G protein coupled receptors (GPCRs). To validate specific sub-families, we chose opsin proteins, representative GPCRs that confer light sensitivity, and Toll-like receptors, representative non-GPCRs, which function in the immune response, and their ability to communicate with microorganisms. Through detailed structure-function analysis of their ligand-binding pockets and downstream signaling cascades, we selected those candidate remote homologues likely to carry out related functions in the corals. This pipeline may prove generally useful for other non-model organisms, such as to support the growing field of synthetic biology.

Sequence-Order Frequency Matrix - Sampling and Machine learning with Smith-Waterman (SOFM-SMSW) for Protein Remote Homology Detection

Background: Protein Remote Homology Detection (PRHD) is used to find the homologous proteins which are similar in function and structure but sharing low sequence identity. In general, the Sequence-Order Frequency Matrix (SOFM) was used for protein remote homology detection. In the SOFM Top-n-gram (SOFM-Top) algorithm, the probability of substrings was calculated based on the highest probability value of substrings. Moreover, SOFM-Smith Waterman (SOFM-SW) algorithm combines the SOFM with local alignment for protein remote homology detection. However, the computation complexity of SOFM based PRHD is high since it processes all protein sequences in SOFM.Objective: Sequence-Order Frequency Matrix - Sampling and Machine learning with Smith-Waterman (SOFM-SMSW) algorithm is proposed for predicting the protein remote homology. The SOFM-SMSW algorithm used the PVS method to select the optimum target sequences based on the uniform distribution measure.Method: This research work considers the most important sequences for PRHD by introducing Proportional Volume Sampling (PVS). After sampling the protein sequences, a feature vector is constructed and labeling is performed based on the concatenation between two protein sequences. Then, a substitution score which represents the structural alignment is learned using k-Nearest Neighbor (k-NN). Based on the learned substitution score and alignment score, the protein homology is detected using Smith-Waterman algorithm and Support Vector Machine (SVM). By selecting the most important sequences, the accuracy of PRHD is improved and the computational complexity for PRHD is reduced by using structural alignment along with the local alignment.Results: The performance of the proposed SOFM-SMSW algorithm is tested with SCOP database and it has been compared with various existing algorithms such as SVM Top-N-gram, SVM pairwise, GPkernal, Long Short-Term Memory (LSTM), SOFM Top-N-gram and SOFM-SW. Conclusion: The experimental results illustrate that the proposed SOFM-SMSW algorithm has better accuracy, precision, recall, ROC and ROC 50 for PRHD than the other existing algorithms.

PHROG: families of prokaryotic virus proteins clustered using remote homology

Viruses are abundant, diverse and ancestral biological entities. Their diversity is high, both in terms of the number of different protein families encountered and in the sequence heterogeneity of each protein family. The recent increase in sequenced viral genomes constitutes a great opportunity to gain new insights into this diversity and consequently urges the development of annotation resources to help functional and comparative analysis. Here, we introduce PHROG (Prokaryotic Virus Remote Homologous Groups), a library of viral protein families generated using a new clustering approach based on remote homology detection by HMM profile-profile comparisons. Considering 17 473 reference (pro)viruses of prokaryotes, 868 340 of the total 938 864 proteins were grouped into 38 880 clusters that proved to be a 2-fold deeper clustering than using a classical strategy based on BLAST-like similarity searches, and yet to remain homogeneous. Manual inspection of similarities to various reference sequence databases led to the annotation of 5108 clusters (containing 50.6 % of the total protein dataset) with 705 different annotation terms, included in 9 functional categories, specifically designed for viruses. Hopefully, PHROG will be a useful tool to better annotate future prokaryotic viral sequences thus helping the scientific community to better understand the evolution and ecology of these entities.

Protein Structural Alignments From Sequence

Computing sequence similarity is a fundamental task in biology, with alignment forming the basis for the annotation of genes and genomes and providing the core data structures for evolutionary analysis. Standard approaches are a mainstay of modern molecular biology and rely on variations of edit distance to obtain explicit alignments between pairs of biological sequences. However, sequence alignment algorithms struggle with remote homology tasks and cannot identify similarities between many pairs of proteins with similar structures and likely homology. Recent work suggests that using machine learning language models can improve remote homology detection. To this end, we introduce DeepBLAST, that obtains explicit alignments from residue embeddings learned from a protein language model integrated into an end-to-end differentiable alignment framework. This approach can be accelerated on the GPU architectures and outperforms conventional sequence alignment techniques in terms of both speed and accuracy when identifying structurally similar proteins.