DeepBrain: Functional Representation of Neural In-Situ Hybridization Images for Gene Ontology Classification Using Deep Convolutional Autoencoders

This paper presents a novel deep learning-based method for learning a functional representation of mammalian neural images. The method uses a deep convolutional denoising autoencoder (CDAE) for generating an invariant, compact representation of in situ hybridization (ISH) images. While most existing methods for bio-imaging analysis were not developed to handle images with highly complex anatomical structures, the results presented in this paper show that functional representation extracted by CDAE can help learn features of functional gene ontology categories for their classification in a highly accurate manner. Using this CDAE representation, our method outperforms the previous state-of-the-art classification rate, by improving the average AUC from 0.92 to 0.98, i.e., achieving 75% reduction in error. The method operates on input images that were downsampled significantly with respect to the original ones to make it computationally feasible

Synthetic Gene Circuits: Design with Directed Evolution

Synthetic circuits offer great promise for generating insights into nature's underlying design principles or forward engineering novel biotechnology applications. However, construction of these circuits is not straightforward. Synthetic circuits generally consist of components optimized to function in their natural context, not in the context of the synthetic circuit. Combining mathematical modeling with directed evolution offers one promising means for addressing this problem. Modeling identifies mutational targets and limits the evolutionary search space for directed evolution, which alters circuit performance without the need for detailed biophysical information. This review examines strategies for integrating modeling and directed evolution and discusses the utility and limitations of available methods

Genetical genomics: spotlight on QTL hotspots

No abstract available

DACH1: its role as a classifier of long term good prognosis in luminal breast cancer

Background: Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. Materials and methods: A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER- associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Results: Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p , 0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p , 0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Conclusion: Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy

Cyclin-dependent kinases as drug targets for cell growth and proliferation disorders. A role for systems biology approach in drug development. Part II - CDKs as drug targets in hypertrophic cell growth. Modelling of drugs targeting CDKs

Cyclin-dependent kinases (CDKs) are key regulators of cell growth and proliferation. Impaired regulation of their activity leads to various diseases such as cancer and heart hypertrophy. Consequently, a number of CDKs are considered as targets for drug discovery. We review the development of inhibitors of CDK2 as anti-cancer drugs in the first part of the paper and in the second part, respectively, the development of inhibitors of CDK9 as potential therapeutics for heart hypertrophy. We argue that the above diseases are systems biology, or network diseases. In order to fully understand the complexity of the cell growth and proliferation disorders, in addition to experimental sciences, a systems biology approach, involving mathematical and computational modelling ought to be employed

Biomolecular network querying: a promising approach in systems biology

The rapid accumulation of various network-related data from multiple species and conditions (e.g. disease versus normal) provides unprecedented opportunities to study the function and evolution of biological systems. Comparison of biomolecular networks between species or conditions is a promising approach to understanding the essential mechanisms used by living organisms. Computationally, the basic goal of this network comparison or 'querying' is to uncover identical or similar subnetworks by mapping the queried network (e.g. a pathway or functional module) to another network or network database. Such comparative analysis may reveal biologically or clinically important pathways or regulatory networks. In particular, we argue that user-friendly tools for network querying will greatly enhance our ability to study the fundamental properties of biomolecular networks at a system-wide level

Mining and state-space modeling and verification of sub-networks from large-scale biomolecular networks

<p>Abstract</p> <p>Background</p> <p>Biomolecular networks dynamically respond to stimuli and implement cellular function. Understanding these dynamic changes is the key challenge for cell biologists. As biomolecular networks grow in size and complexity, the model of a biomolecular network must become more rigorous to keep track of all the components and their interactions. In general this presents the need for computer simulation to manipulate and understand the biomolecular network model.</p> <p>Results</p> <p>In this paper, we present a novel method to model the regulatory system which executes a cellular function and can be represented as a biomolecular network. Our method consists of two steps. First, a novel scale-free network clustering approach is applied to the large-scale biomolecular network to obtain various sub-networks. Second, a state-space model is generated for the sub-networks and simulated to predict their behavior in the cellular context. The modeling results represent <it>hypotheses </it>that are tested against high-throughput data sets (microarrays and/or genetic screens) for both the natural system and perturbations. Notably, the dynamic modeling component of this method depends on the automated network structure generation of the first component and the sub-network clustering, which are both essential to make the solution tractable.</p> <p>Conclusion</p> <p>Experimental results on time series gene expression data for the human cell cycle indicate our approach is promising for sub-network mining and simulation from large-scale biomolecular network.</p