7,558 research outputs found
Identification of disease-causing genes using microarray data mining and gene ontology
Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes.
Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results.
Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth.
Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
Machine learning-guided directed evolution for protein engineering
Machine learning (ML)-guided directed evolution is a new paradigm for
biological design that enables optimization of complex functions. ML methods
use data to predict how sequence maps to function without requiring a detailed
model of the underlying physics or biological pathways. To demonstrate
ML-guided directed evolution, we introduce the steps required to build ML
sequence-function models and use them to guide engineering, making
recommendations at each stage. This review covers basic concepts relevant to
using ML for protein engineering as well as the current literature and
applications of this new engineering paradigm. ML methods accelerate directed
evolution by learning from information contained in all measured variants and
using that information to select sequences that are likely to be improved. We
then provide two case studies that demonstrate the ML-guided directed evolution
process. We also look to future opportunities where ML will enable discovery of
new protein functions and uncover the relationship between protein sequence and
function.Comment: Made significant revisions to focus on aspects most relevant to
applying machine learning to speed up directed evolutio
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Multi-class protein fold classification using a new ensemble machine learning approach.
Protein structure classification represents an important process in understanding the associations
between sequence and structure as well as possible functional and evolutionary relationships.
Recent structural genomics initiatives and other high-throughput experiments have populated the
biological databases at a rapid pace. The amount of structural data has made traditional methods
such as manual inspection of the protein structure become impossible. Machine learning has been
widely applied to bioinformatics and has gained a lot of success in this research area. This work
proposes a novel ensemble machine learning method that improves the coverage of the classifiers
under the multi-class imbalanced sample sets by integrating knowledge induced from different base
classifiers, and we illustrate this idea in classifying multi-class SCOP protein fold data. We have
compared our approach with PART and show that our method improves the sensitivity of the
classifier in protein fold classification. Furthermore, we have extended this method to learning over
multiple data types, preserving the independence of their corresponding data sources, and show
that our new approach performs at least as well as the traditional technique over a single joined
data source. These experimental results are encouraging, and can be applied to other bioinformatics
problems similarly characterised by multi-class imbalanced data sets held in multiple data
sources
Automatic document classification of biological literature
Background: Document classification is a wide-spread problem with many applications, from organizing search engine snippets to spam filtering. We previously described Textpresso, a text-mining system for biological literature, which marks up full text according to a shallow ontology that includes terms of biological interest. This project investigates document classification in the context of biological literature, making use of the Textpresso markup of a corpus of Caenorhabditis elegans literature.
Results: We present a two-step text categorization algorithm to classify a corpus of C. elegans papers. Our classification method first uses a support vector machine-trained classifier, followed by a novel, phrase-based clustering algorithm. This clustering step autonomously creates cluster labels that are descriptive and understandable by humans. This clustering engine performed better on a standard test-set (Reuters 21578) compared to previously published results (F-value of 0.55 vs. 0.49), while producing cluster descriptions that appear more useful. A web interface allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept.
Conclusions: We have demonstrated a simple method to classify biological documents that embodies an improvement over current methods. While the classification results are currently optimized for Caenorhabditis elegans papers by human-created rules, the classification engine can be adapted to different types of documents. We have demonstrated this by presenting a web interface that allows researchers to quickly navigate through the hierarchy and look for documents that belong to a specific concept
The Parallelism Motifs of Genomic Data Analysis
Genomic data sets are growing dramatically as the cost of sequencing
continues to decline and small sequencing devices become available. Enormous
community databases store and share this data with the research community, but
some of these genomic data analysis problems require large scale computational
platforms to meet both the memory and computational requirements. These
applications differ from scientific simulations that dominate the workload on
high end parallel systems today and place different requirements on programming
support, software libraries, and parallel architectural design. For example,
they involve irregular communication patterns such as asynchronous updates to
shared data structures. We consider several problems in high performance
genomics analysis, including alignment, profiling, clustering, and assembly for
both single genomes and metagenomes. We identify some of the common
computational patterns or motifs that help inform parallelization strategies
and compare our motifs to some of the established lists, arguing that at least
two key patterns, sorting and hashing, are missing
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