DeePSLiM: A Deep Learning Approach to Identify Predictive Short-linear Motifs for Protein Sequence Classification

With the increasing quantity of biological data, it is important to develop algorithms that can quickly find patterns in large databases of DNA, RNA and protein sequences. Previous research has been very successful at applying deep learning methods to the problems of motif detection as well as classification of biological sequences. There are, however, limitations to these approaches. Most are limited to finding motifs of a single length. In addition, most research has focused on DNA and RNA, both of which use a four letter alphabet. A few of these have attempted to apply deep learning methods on the larger, twenty letter, alphabet of proteins. We present an enhanced deep learning model, called DeePSLiM, capable of detecting predictive, short linear motifs (SLiM) in protein sequences. The model is a shallow network that can be trained quickly on large amounts of data. The SLiMs are predictive because they can be used to classify the sequences into their respective families. The model was able to reach scores of 94.5% on accuracy, precision, recall, F1-Score and Matthews-correlation coefficient, as well as 99.9% area under the receiver operator characteristic curve (AUROC)

Classification of Protein Kinases on the Basis of Both Kinase and Non-Kinase Regions

BACKGROUND: Protein phosphorylation is a generic way to regulate signal transduction pathways in all kingdoms of life. In many organisms, it is achieved by the large family of Ser/Thr/Tyr protein kinases which are traditionally classified into groups and subfamilies on the basis of the amino acid sequence of their catalytic domains. Many protein kinases are multi-domain in nature but the diversity of the accessory domains and their organization are usually not taken into account while classifying kinases into groups or subfamilies. METHODOLOGY: Here, we present an approach which considers amino acid sequences of complete gene products, in order to suggest refinements in sets of pre-classified sequences. The strategy is based on alignment-free similarity scores and iterative Area Under the Curve (AUC) computation. Similarity scores are computed by detecting common patterns between two sequences and scoring them using a substitution matrix, with a consistent normalization scheme. This allows us to handle full-length sequences, and implicitly takes into account domain diversity and domain shuffling. We quantitatively validate our approach on a subset of 212 human protein kinases. We then employ it on the complete repertoire of human protein kinases and suggest few qualitative refinements in the subfamily assignment stored in the KinG database, which is based on catalytic domains only. Based on our new measure, we delineate 37 cases of potential hybrid kinases: sequences for which classical classification based entirely on catalytic domains is inconsistent with the full-length similarity scores computed here, which implicitly consider multi-domain nature and regions outside the catalytic kinase domain. We also provide some examples of hybrid kinases of the protozoan parasite Entamoeba histolytica. CONCLUSIONS: The implicit consideration of multi-domain architectures is a valuable inclusion to complement other classification schemes. The proposed algorithm may also be employed to classify other families of enzymes with multi-domain architecture

Machine learning and data-parallel processing for viral metagenomics

More than 2 million cancer cases around the world each year are caused by viruses. In addition, there are epidemiological indications that other cancer-associated viruses may also exist. However, the identification of highly divergent and yet unknown viruses in human biospecimens is one of the biggest challenges in bio- informatics. Modern-day Next Generation Sequencing (NGS) technologies can be used to directly sequence biospecimens from clinical cohorts with unprecedented speed and depth. These technologies are able to generate billions of bases with rapidly decreasing cost but current bioinformatics tools are inefficient to effectively process these massive datasets. Thus, the objective of this thesis was to facilitate both the detection of highly divergent viruses among generated sequences as well as large-scale analysis of human metagenomic datasets. To re-analyze human sample-derived sequences that were classified as being of “unknown” origin by conventional alignment-based methods, we used a meth- odology based on profile Hidden Markov Models (HMM) which can capture evolutionary changes by using multiple sequence alignments. We thus identified 510 sequences that were classified as distantly related to viruses. Many of these sequences were homologs to large viruses such as Herpesviridae and Mimiviridae but some of them were also related to small circular viruses such as Circoviridae. We found that bioinformatics analysis using viral profile HMM is capable of extending the classification of previously unknown sequences and consequently the detection of viruses in biospecimens from humans. Different organisms use synonymous codons differently to encode the same amino acids. To investigate whether codon usage bias could predict the presence of virus in metagenomic sequencing data originating from human samples, we trained Random Forest and Artificial Neural Networks based on Relative Synonymous Codon Usage (RSCU) frequency. Our analysis showed that machine learning tech- niques based on RSCU could identify putative viral sequences with area under the ROC curve of 0.79 and provide important information for taxonomic classification. For identification of viral genomes among raw metagenomic sequences, we devel- oped the tool ViraMiner, a deep learning-based method which uses Convolutional Neural Networks with two convolutional branches. Using 300 base-pair length sequences, ViraMiner achieved 0.923 area under the ROC curve which is con- siderably improved performance in comparison with previous machine learning methods for virus sequence classification. The proposed architecture, to the best of our knowledge, is the first deep learning tool which can detect viral genomes on raw metagenomic sequences originating from a variety of human samples. To enable large-scale analysis of massive metagenomic sequencing data we used Apache Hadoop and Apache Spark to develop ViraPipe, a scalable parallel bio- informatics pipeline for viral metagenomics. Comparing ViraPipe (executed on 23 nodes) with the sequential pipeline (executed on a single node) was 11 times faster in the metagenome analysis. The new distributed workflow contains several standard bioinformatics tools and can scale to terabytes of data by accessing more computer power from the nodes. To analyze terabytes of RNA-seq data originating from head and neck squamous cell carcinoma samples, we used our parallel bioinformatics pipeline ViraPipe and the most recent version of the HPV sequence database. We detected transcription of HPV viral oncogenes in 92/500 cancers. HPV 16 was the most important HPV type, followed by HPV 33 as the second most common infection. If these cancers are indeed caused by HPV, we estimated that vaccination might prevent about 36 000 head and neck cancer cases in the United States every year. In conclusion, the work in this thesis improves the prospects for biomedical researchers to classify the sequence contents of ultra-deep datasets, conduct large- scale analysis of metagenome studies, and detect presence of viral genomes in human biospecimens. Hopefully, this work will contribute to our understanding of biodiversity of viruses in humans which in turn can help exploring infectious causes of human disease

Zenseact Open Dataset: A large-scale and diverse multimodal dataset for autonomous driving

Existing datasets for autonomous driving (AD) often lack diversity and long-range capabilities, focusing instead on 360{\deg} perception and temporal reasoning. To address this gap, we introduce Zenseact Open Dataset (ZOD), a large-scale and diverse multimodal dataset collected over two years in various European countries, covering an area 9x that of existing datasets. ZOD boasts the highest range and resolution sensors among comparable datasets, coupled with detailed keyframe annotations for 2D and 3D objects (up to 245m), road instance/semantic segmentation, traffic sign recognition, and road classification. We believe that this unique combination will facilitate breakthroughs in long-range perception and multi-task learning. The dataset is composed of Frames, Sequences, and Drives, designed to encompass both data diversity and support for spatio-temporal learning, sensor fusion, localization, and mapping. Frames consist of 100k curated camera images with two seconds of other supporting sensor data, while the 1473 Sequences and 29 Drives include the entire sensor suite for 20 seconds and a few minutes, respectively. ZOD is the only large-scale AD dataset released under a permissive license, allowing for both research and commercial use. More information, and an extensive devkit, can be found at https://zod.zenseact.comComment: International Conference on Computer Vision (ICCV) 202

Single-Input Signature Register-Based Time Delay Reservoir

Machine learning continues to play a critical role in our society. The ability to automatically identify intricate relationships in large volumes of data has proven incredibly useful for problems such as automatic speech recognition and image processing. In particular, neural networks have become increasingly popular in a wide set of application domains, given their ability to solve complex problems and process high-dimensional data. However, the impressive performance of state-of-the-art neural networks comes at the cost of large area and power consumption for the computation resources used in training and inference. As a result, a growing area of research concerns hardware implementations of neural networks. This work proposes a hardware-friendly design for a time-delay reservoir (TDR), a type of recurrent neural network. TDRs represent one class of reservoir computing neural network topologies, which employ random spatio-temporal feature extraction from time series data in order to produce a linearly separable set of features. Reservoir computing topologies differ from traditional recurrent neural networks because their recurrent weights are fixed, and the only the feedforward output weights need to be trained, usually with linear regression. Previous work on TDRs includes photonic implementation, software implementation, and both digital and analog electronic implementations. This work adds to the body of previous research by exploring the design space of a novel TDR based on single-input signature registers (SISRs), which are common digital circuits used for built-in self-test. The work is motivated by the structural similarity (delayed feedback loop) between TDRs and SISRs, and the possibility of dual-purpose of SISRs for conventional testing as well as machine learning within a single chip. The proposed designs can perform classification on multivariate datasets and perform better than a traditional TDR with quantized reservoir states for parity check, MNIST classification, and temperature prediction tasks. Classification accuracies of up to 100% were observed for some configurations of the SISR for the parity check task and accuracies of up to 85% were observed for MNIST classification. We also observe overfitting on a temperature prediction task with longer data sequences and provide analyses of the results based on the reservoir dynamics, as measured by the rate of divergence between SISR states and the SISR period

Bounded Coordinate-Descent for Biological Sequence Classification in High Dimensional Predictor Space

We present a framework for discriminative sequence classification where the learner works directly in the high dimensional predictor space of all subsequences in the training set. This is possible by employing a new coordinate-descent algorithm coupled with bounding the magnitude of the gradient for selecting discriminative subsequences fast. We characterize the loss functions for which our generic learning algorithm can be applied and present concrete implementations for logistic regression (binomial log-likelihood loss) and support vector machines (squared hinge loss). Application of our algorithm to protein remote homology detection and remote fold recognition results in performance comparable to that of state-of-the-art methods (e.g., kernel support vector machines). Unlike state-of-the-art classifiers, the resulting classification models are simply lists of weighted discriminative subsequences and can thus be interpreted and related to the biological problem