Yeast gene CMR1/YDL156W is consistently co-expressed with genes participating in DNA-metabolic processes in a variety of stringent clustering experiments

© 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.The binarization of consensus partition matrices (Bi-CoPaM) method has, among its unique features, the ability to perform ensemble clustering over the same set of genes from multiple microarray datasets by using various clustering methods in order to generate tunable tight clusters. Therefore, we have used the Bi-CoPaM method to the most synchronized 500 cell-cycle-regulated yeast genes from different microarray datasets to produce four tight, specific and exclusive clusters of co-expressed genes. We found 19 genes formed the tightest of the four clusters and this included the gene CMR1/YDL156W, which was an uncharacterized gene at the time of our investigations. Two very recent proteomic and biochemical studies have independently revealed many facets of CMR1 protein, although the precise functions of the protein remain to be elucidated. Our computational results complement these biological results and add more evidence to their recent findings of CMR1 as potentially participating in many of the DNA-metabolism processes such as replication, repair and transcription. Interestingly, our results demonstrate the close co-expressions of CMR1 and the replication protein A (RPA), the cohesion complex and the DNA polymerases α, δ and ɛ, as well as suggest functional relationships between CMR1 and the respective proteins. In addition, the analysis provides further substantial evidence that the expression of the CMR1 gene could be regulated by the MBF complex. In summary, the application of a novel analytic technique in large biological datasets has provided supporting evidence for a gene of previously unknown function, further hypotheses to test, and a more general demonstration of the value of sophisticated methods to explore new large datasets now so readily generated in biological experiments.National Institute for Health Researc

Bisociative knowledge discovery for microarray data analysis

Peer reviewe

BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation

We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be

Big Data Transforms Discovery-Utilization Therapeutics Continuum.

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization

Using rule extraction to improve the comprehensibility of predictive models.

Whereas newer machine learning techniques, like artifficial neural net-works and support vector machines, have shown superior performance in various benchmarking studies, the application of these techniques remains largely restricted to research environments. A more widespread adoption of these techniques is foiled by their lack of explanation capability which is required in some application areas, like medical diagnosis or credit scoring. To overcome this restriction, various algorithms have been proposed to extract a meaningful description of the underlying `blackbox' models. These algorithms' dual goal is to mimic the behavior of the black box as closely as possible while at the same time they have to ensure that the extracted description is maximally comprehensible. In this research report, we first develop a formal definition of`rule extraction and comment on the inherent trade-off between accuracy and comprehensibility. Afterwards, we develop a taxonomy by which rule extraction algorithms can be classiffied and discuss some criteria by which these algorithms can be evaluated. Finally, an in-depth review of the most important algorithms is given.This report is concluded by pointing out some general shortcomings of existing techniques and opportunities for future research.Models; Model; Algorithms; Criteria; Opportunities; Research; Learning; Neural networks; Networks; Performance; Benchmarking; Studies; Area; Credit; Credit scoring; Behavior; Time;

New trends in data mining.

Trends; Data; Data mining;

Proteomics

Despite years of preclinical development, biological interventions designed to treat complex diseases such as asthma often fail in phase III clinical trials. These failures suggest that current methods to analyze biomedical data might be missing critical aspects of biological complexity such as the assumption that cases and controls come from homogeneous distributions. Here we discuss why and how methods from the rapidly evolving field of visual analytics can help translational teams (consisting of biologists, clinicians, and bioinformaticians) to address the challenge of modeling and inferring heterogeneity in the proteomic and phenotypic profiles of patients with complex diseases. Because a primary goal of visual analytics is to amplify the cognitive capacities of humans for detecting patterns in complex data, we begin with an overview of the cognitive foundations for the field of visual analytics. Next, we organize the primary ways in which a specific form of visual analytics called networks has been used to model and infer biological mechanisms, which help to identify the properties of networks that are particularly useful for the discovery and analysis of proteomic heterogeneity in complex diseases. We describe one such approach called subject-protein networks, and demonstrate its application on two proteomic datasets. This demonstration provides insights to help translational teams overcome theoretical, practical, and pedagogical hurdles for the widespread use of subject-protein networks for analyzing molecular heterogeneities, with the translational goal of designing biomarker-based clinical trials, and accelerating the development of personalized approaches to medicine.1UL1TR000071/TR/NCATS NIH HHS/United StatesHHSN268201000037C/HV/NHLBI NIH HHS/United StatesHHSN268201000037C-0-0-1/PHS HHS/United StatesKL2 TR000072/TR/NCATS NIH HHS/United StatesR21 OH009441/OH/NIOSH CDC HHS/United StatesR21OH009441-01A2/OH/NIOSH CDC HHS/United StatesUL1 TR000071/TR/NCATS NIH HHS/United States2015-06-18T00:00:00Z25684269PMC447133

On Cognitive Preferences and the Plausibility of Rule-based Models

It is conventional wisdom in machine learning and data mining that logical models such as rule sets are more interpretable than other models, and that among such rule-based models, simpler models are more interpretable than more complex ones. In this position paper, we question this latter assumption by focusing on one particular aspect of interpretability, namely the plausibility of models. Roughly speaking, we equate the plausibility of a model with the likeliness that a user accepts it as an explanation for a prediction. In particular, we argue that, all other things being equal, longer explanations may be more convincing than shorter ones, and that the predominant bias for shorter models, which is typically necessary for learning powerful discriminative models, may not be suitable when it comes to user acceptance of the learned models. To that end, we first recapitulate evidence for and against this postulate, and then report the results of an evaluation in a crowd-sourcing study based on about 3.000 judgments. The results do not reveal a strong preference for simple rules, whereas we can observe a weak preference for longer rules in some domains. We then relate these results to well-known cognitive biases such as the conjunction fallacy, the representative heuristic, or the recogition heuristic, and investigate their relation to rule length and plausibility.Comment: V4: Another rewrite of section on interpretability to clarify focus on plausibility and relation to interpretability, comprehensibility, and justifiabilit