Detecting Clustered Independent Rare Variant Associations Using Genetic Algorithms.

The availability of an increasing collection of sequencing data provides the opportunity to study genetic variation with an unprecedented level of detail. There is much interest in uncovering the role of rare variants and their contribution to disease. However, detecting associations of rare variants with small minor allele frequencies (MAF) and modest effects remains a challenge for rare variant association methods. Due to this low signal-to-noise ratio, most methods are underpowered to detect associations even when conducting rare variant association tests at the gene level. We present a new method for detecting rare variant associations. The algorithm consists of two steps. In the first step, a genetic algorithm searches for a promising genomic region containing a collection of genes with causal rare variants. In the second step, a genetic algorithm aims at removing false positives from the located genomic region. We tested the proposed method with a collection of datasets obtained from real exome data. The proposed method possesses sufficient power for detecting associations of rare variants with complex phenotypes. This method can be used for studying the contribution of rare variants with complex disease, particularly in cases where single-variant or gene-based tests are underpowered.

Benchmarking machine learning models for late-onset alzheimer's disease prediction from genomic data.

BACKGROUND: Late-Onset Alzheimer's Disease (LOAD) is a leading form of dementia. There is no effective cure for LOAD, leaving the treatment efforts to depend on preventive cognitive therapies, which stand to benefit from the timely estimation of the risk of developing the disease. Fortunately, a growing number of Machine Learning methods that are well positioned to address this challenge are becoming available. RESULTS: We conducted systematic comparisons of representative Machine Learning models for predicting LOAD from genetic variation data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Our experimental results demonstrate that the classification performance of the best models tested yielded ∼72% of area under the ROC curve. CONCLUSIONS: Machine learning models are promising alternatives for estimating the genetic risk of LOAD. Systematic machine learning model selection also provides the opportunity to identify new genetic markers potentially associated with the disease.

Acoustic sequences in non-human animals: a tutorial review and prospectus.

Animal acoustic communication often takes the form of complex sequences, made up of multiple distinct acoustic units. Apart from the well-known example of birdsong, other animals such as insects, amphibians, and mammals (including bats, rodents, primates, and cetaceans) also generate complex acoustic sequences. Occasionally, such as with birdsong, the adaptive role of these sequences seems clear (e.g. mate attraction and territorial defence). More often however, researchers have only begun to characterise - let alone understand - the significance and meaning of acoustic sequences. Hypotheses abound, but there is little agreement as to how sequences should be defined and analysed. Our review aims to outline suitable methods for testing these hypotheses, and to describe the major limitations to our current and near-future knowledge on questions of acoustic sequences. This review and prospectus is the result of a collaborative effort between 43 scientists from the fields of animal behaviour, ecology and evolution, signal processing, machine learning, quantitative linguistics, and information theory, who gathered for a 2013 workshop entitled, 'Analysing vocal sequences in animals'. Our goal is to present not just a review of the state of the art, but to propose a methodological framework that summarises what we suggest are the best practices for research in this field, across taxa and across disciplines. We also provide a tutorial-style introduction to some of the most promising algorithmic approaches for analysing sequences. We divide our review into three sections: identifying the distinct units of an acoustic sequence, describing the different ways that information can be contained within a sequence, and analysing the structure of that sequence. Each of these sections is further subdivided to address the key questions and approaches in that area. We propose a uniform, systematic, and comprehensive approach to studying sequences, with the goal of clarifying research terms used in different fields, and facilitating collaboration and comparative studies. Allowing greater interdisciplinary collaboration will facilitate the investigation of many important questions in the evolution of communication and sociality.

A computer simulation model of Wolbachia invasion for disease vector population modification.

BACKGROUND: Wolbachia invasion has been proved to be a promising alternative for controlling vector-borne diseases, particularly Dengue fever. Creating computer models that can provide insight into how vector population modification can be achieved under different conditions would be most valuable for assessing the efficacy of control strategies for this disease. METHODS: In this paper, we present a computer model that simulates the behavior of native mosquito populations after the introduction of mosquitoes infected with the Wolbachia bacteria. We studied how different factors such as fecundity, fitness cost of infection, migration rates, number of populations, population size, and number of introduced infected mosquitoes affect the spread of the Wolbachia bacteria among native mosquito populations. RESULTS: Two main scenarios of the island model are presented in this paper, with infected mosquitoes introduced into the largest source population and peripheral populations. Overall, the results are promising; Wolbachia infection spreads among native populations and the computer model is capable of reproducing the results obtained by mathematical models and field experiments. CONCLUSIONS: Computer models can be very useful for gaining insight into how Wolbachia invasion works and are a promising alternative for complementing experimental and mathematical approaches for vector-borne disease control.

Computer simulation on disease vector population replacement driven by the maternal effect dominant embryonic arrest.

In this chapter, we present a series of computer simulations on the genetic modification of disease vectors. We compared the effectiveness of two techniques of genetic modification, transposable elements and maternal effect dominant embryonic arrest (MEDEA). A gene drive mechanism based on MEDEA is introduced in the population to confer immunity to individuals. Experimental results suggested that the genetic maternal effects could be necessary for the effectiveness of a disease control strategy based on the genetic modification of vectors.

Inferring modules of functionally interacting proteins using the Bond Energy Algorithm.

BACKGROUND: Non-homology based methods such as phylogenetic profiles are effective for predicting functional relationships between proteins with no considerable sequence or structure similarity. Those methods rely heavily on traditional similarity metrics defined on pairs of phylogenetic patterns. Proteins do not exclusively interact in pairs as the final biological function of a protein in the cellular context is often hold by a group of proteins. In order to accurately infer modules of functionally interacting proteins, the consideration of not only direct but also indirect relationships is required. In this paper, we used the Bond Energy Algorithm (BEA) to predict functionally related groups of proteins. With BEA we create clusters of phylogenetic profiles based on the associations of the surrounding elements of the analyzed data using a metric that considers linked relationships among elements in the data set. RESULTS: Using phylogenetic profiles obtained from the Cluster of Orthologous Groups of Proteins (COG) database, we conducted a series of clustering experiments using BEA to predict (upper level) relationships between profiles. We evaluated our results by comparing with COG's functional categories, And even more, with the experimentally determined functional relationships between proteins provided by the DIP and ECOCYC databases. Our results demonstrate that BEA is capable of predicting meaningful modules of functionally related proteins. BEA outperforms traditionally used clustering methods, such as k-means and hierarchical clustering by predicting functional relationships between proteins with higher accuracy. CONCLUSION: This study shows that the linked relationships of phylogenetic profiles obtained by BEA is useful for detecting functional associations between profiles and extending functional modules not found by traditional methods. BEA is capable of detecting relationship among phylogenetic patterns by linking them through a common element shared in a group. Additionally, we discuss how the proposed method may become more powerful if other criteria to classify different levels of protein functional interactions, as gene neighborhood or protein fusion information, is provided.

Automated species recognition of antbirds in a Mexican rainforest using hidden Markov models.

Behavioral and ecological studies would benefit from the ability to automatically identify species from acoustic recordings. The work presented in this article explores the ability of hidden Markov models to distinguish songs from five species of antbirds that share the same territory in a rainforest environment in Mexico. When only clean recordings were used, species recognition was nearly perfect, 99.5%. With noisy recordings, performance was lower but generally exceeding 90%. Besides the quality of the recordings, performance has been found to be heavily influenced by a multitude of factors, such as the size of the training set, the feature extraction method used, and number of states in the Markov model. In general, training with noisier data also improved recognition in test recordings, because of an increased ability to generalize. Considerations for improving performance, including beamforming with sensor arrays and design of preprocessing methods particularly suited for bird songs, are discussed. Combining sensor network technology with effective event detection and species identification algorithms will enable observation of species interactions at a spatial and temporal resolution that is simply impossible with current tools. Analysis of animal behavior through real-time tracking of individuals and recording of large amounts of data with embedded devices in remote locations is thus a realistic goal.