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Motivation: Modern automated laboratories need substantial data management solutions to both store and make accessible the details of the experiments they perform. To be useful, a modern Laboratory Information Management System (LIMS) should be flexible and easily extensible to support evolving laboratory requirements, and should be based on the solid foundations of a robust, well-designed database. We have developed such a database schema to support an automated laboratory that performs experiments in systems biology and high-throughput screening.Results: We describe the design of the database schema (AutoLabDB), detailing the main features and describing why we believe it will be relevant to LIMS manufacturers or custom builders. This database has been developed to support two large automated Robot Scientist systems over the last 5 years, where it has been used as the basis of an LIMS that helps to manage both the laboratory and all the experiment data produced.Availability and implementation: The database schema has been made available as open source (BSD license), so that others may use, extend and improve it to meet their own needs. Example software interfaces to the database are also provided. http://autolabdb.sourceforge.net/Contact: afc@aber.ac.uk [ABSTRACT FROM PUBLISHER]

Summary: We present Goldilocks: a Python package providing functionality for collecting summary statistics, identifying shifts in variation, discovering outlier regions and locating and extracting interesting regions from one or more arbitrary genomes for further analysis, for a userprovided definition of interesting. Availability and implementation: Goldilocks is freely available open-source software distributed under the MIT licence. Source code is hosted publicly at https://github.com/SamStudio8/goldilocks and the package may also be installed using pip install goldilocks. Documentation can be found at https://goldilocks.readthedocs.org. [ABSTRACT FROM AUTHOR]

We wished to quantify the state-of-the-art of our understanding of clusters in microarray data. To do this we systematically compared the clusters produced on sets of microarray data using a representative set of clustering algorithms (hierarchical, k-means, and a modified version of QTCLUST) with the annotation schemes MIPS, GeneOntology and GenProtEC. We assumed that if a cluster reflected known biology its members would share related ontological annotations. This assumption is the basis of "guilt-by-association" and is commonly used to assign the putative function of proteins. To statistically measure the relationship between cluster and annotation we developed a new predictive discriminatory measure. We found that the clusters found in microarray data do not in general agree with functional annotation classes. Although many statistically significant relationships can be found, the majority of clusters are not related to known biology (as described in annotation ontologies). This implies that use of guilt-by-association is not supported by annotation ontologies. Depending on the estimate of the amount of noise in the data, our results suggest that bioinformatics has only codified a small proportion of the biological knowledge required to understand microarray data. The annotated clusters can be found at http://www.aber.ac.uk/compsci/Research/bio/dss/gba/. [ABSTRACT FROM AUTHOR]

How does scientific research affect the world around us? Being able to answer this question is of great importance in order to appropriately channel efforts and resources in science. The impact by scientists in academia is currently measured by citation based metrics such as h-index, i-index and citation counts. These academic metrics aim to represent the dissemination of knowledge among scientists rather than the impact of the research on the wider world. In this work we are interested in measuring scientific impact beyond academia, on the economy, society, health and legislation (comprehensive impact). Indeed scientists are asked to demonstrate evidence of such comprehensive impact by authoring case studies in the context of the Research Excellence Framework (REF). We first investigate the extent to which existing citation based metrics can be indicative of comprehensive impact. We have collected all recent REF impact case studies from 2014 and we have linked these to papers in citation networks that we constructed and derived from CiteSeerX, arXiv and PubMed Central using a number of text processing and information retrieval techniques. We have demonstrated that existing citation-based metrics for impact measurement do not correlate well with REF impact results. We also consider metrics of online attention surrounding scientific works, such as those provided by the Altmetric API. We argue that in order to be able to evaluate wider non-academic impact we need to mine information from a much wider set of resources, including social media posts, press releases, news articles and political debates stemming from academic work. We also provide our data as a free and reusable collection for further analysis, including the PubMed citation network and the correspondence between REF case studies, grant applications and the academic literature. [ABSTRACT FROM AUTHOR]

The body of peer-reviewed papers on enteric methane mitigation strategies in ruminants is rapidly growing and allows for better estimation of the true effect of each strategy though the use of meta-analysis methods. Here we present the development of an online database of measured methane mitigation strategies called MitiGate, currently comprising 412 papers. The database is accessible through an online user-friendly interface that allows data extraction with various levels of aggregation on one hand and data-uploading for submission to the database allowing for future refinement and updates of mitigation estimates as well as providing easy access to relevant data for integration into modelling efforts or policy recommendations. To demonstrate and verify the usefulness of the MitiGate database those studies where methane emissions were expressed per unit of intake (293 papers resulting in 845 treatment comparisons) were used in a meta-analysis. The meta-analysis of the current database estimated the effect size of each of the mitigation strategies as well as the associated variance and measure of heterogeneity. Currently, under-representation of certain strategies, geographic regions and long term studies are the main limitations in providing an accurate quantitative estimation of the mitigation potential of each strategy under varying animal production systems. We have thus implemented the facility for researchers to upload meta-data of their peer reviewed research through a simple input form in the hope that MitiGate will grow into a fully inclusive resource for those wishing to model methane mitigation strategies in ruminants. [ABSTRACT FROM AUTHOR]

Motivation The biases in CoDing Sequence (CDS) prediction tools, which have been based on historic genomic annotations from model organisms, impact our understanding of novel genomes and metagenomes. This hinders the discovery of new genomic information as it results in predictions being biased towards existing knowledge. To date, users have lacked a systematic and replicable approach to identify the strengths and weaknesses of any CDS prediction tool and allow them to choose the right tool for their analysis. Results We present an evaluation framework (ORForise) based on a comprehensive set of 12 primary and 60 secondary metrics that facilitate the assessment of the performance of CDS prediction tools. This makes it possible to identify which performs better for specific use-cases. We use this to assess 15 ab initio - and model-based tools representing those most widely used (historically and currently) to generate the knowledge in genomic databases. We find that the performance of any tool is dependent on the genome being analysed, and no individual tool ranked as the most accurate across all genomes or metrics analysed. Even the top-ranked tools produced conflicting gene collections, which could not be resolved by aggregation. The ORForise evaluation framework provides users with a replicable, data-led approach to make informed tool choices for novel genome annotations and for refining historical annotations. Availability and implementation Code and datasets for reproduction and customisation are available at https://github.com/NickJD/ORForise. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation Population-level genetic variation enables competitiveness and niche specialization in microbial communities. Despite the difficulty in culturing many microbes from an environment, we can still study these communities by isolating and sequencing DNA directly from an environment (metagenomics). Recovering the genomic sequences of all isoforms of a given gene across all organisms in a metagenomic sample would aid evolutionary and ecological insights into microbial ecosystems with potential benefits for medicine and biotechnology. A significant obstacle to this goal arises from the lack of a computationally tractable solution that can recover these sequences from sequenced read fragments. This poses a problem analogous to reconstructing the two sequences that make up the genome of a diploid organism (i.e. haplotypes) but for an unknown number of individuals and haplotypes. Results The problem of single individual haplotyping was first formalized by Lancia et al. in 2001. Now, nearly two decades later, we discuss the complexity of 'haplotyping' metagenomic samples, with a new formalization of Lancia et al.' s data structure that allows us to effectively extend the single individual haplotype problem to microbial communities. This work describes and formalizes the problem of recovering genes (and other genomic subsequences) from all individuals within a complex community sample, which we term the metagenomic individual haplotyping problem. We also provide software implementations for a pairwise single nucleotide variant (SNV) co-occurrence matrix and greedy graph traversal algorithm. Availability and implementation Our reference implementation of the described pairwise SNV matrix (Hansel) and greedy haplotype path traversal algorithm (Gretel) is open source, MIT licensed and freely available online at github.com/samstudio8/hansel and github.com/samstudio8/gretel, respectively. [ABSTRACT FROM AUTHOR]

Promoting replication of models is unarguably a positive step for agent based modelling, as replication promotes rigorous testing. Model replication remains rare, yet is vital to assessing the repeatability of existing agent based models. Notably, more work is needed to assess cross platform and language replication, which represent potential sources of variability between model results. An existing, complex agent based model was replicated using two widely used platforms (NetLogo and Repast). When results generated by the models were compared, the findings differed not only in magnitude but the trends produced by the data, resulting in different conclusions being drawn from each set of model predictions. The variation between the models is believed to be a result of the complexity of encoding a substantial theoretical model in particular programming languages. This highlights the express need to document replication of existing models in order to fully understand the potential limitations to replication. [ABSTRACT FROM AUTHOR]

Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences), or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1) a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2) software to design the method’s primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs) from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome. [ABSTRACT FROM AUTHOR]

Background: Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications. Results: The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C++ with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification. Conclusions: The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design [ABSTRACT FROM AUTHOR]

We review the main components of autonomous scientific discovery, and how they lead to the concept of a Robot Scientist. This is a system which uses techniques from artificial intelligence to automate all aspects of the scientific discovery process: it generates hypotheses from a computer model of the domain, designs experiments to test these hypotheses, runs the physical experiments using robotic systems, analyses and interprets the resulting data, and repeats the cycle. We describe our two prototype Robot Scientists: Adam and Eve. Adam has recently proven the potential of such systems by identifying twelve genes responsible for catalysing specific reactions in the metabolic pathways of the yeast Saccharomyces cerevisiae. This work has been formally recorded in great detail using logic. We argue that the reporting of science needs to become fully formalised and that Robot Scientists can help achieve this. This will make scientific information more reproducible and reusable, and promote the integration of computers in scientific reasoning. We believe the greater automation of both the physical and intellectual aspects of scientific investigations to be essential to the future of science. Greater automation improves the accuracy and reliability of experiments, increases the pace of discovery and, in common with conventional laboratory automation, removes tedious and repetitive tasks from the human scientist. [ABSTRACT FROM AUTHOR]

The article discusses the case for developing robot scientists. Developing robot scientists is said to be simpler than developing general artificial intelligence (AI) systems because the social milieu does not need to be taken into account. Robot scientists apply techniques from AI to automatically execute cycles of scientific experimentation. Increasing the productivity and efficiency of science is identified as the technological motivation for robot scientists.

The basis of science is the hypothetico-deductive method and the recording of experiments in sufficient detail to enable reproducibility. We report the development of Robot Scientist "Adam," which advances the automation of both. Adam has autonomously generated functional genomics hypotheses about the yeast Saccharomyces cerevisiae and experimentally tested these hypotheses by using laboratory automation. We have confirmed Adam's conclusions through manual experiments. To describe Adam's research, we have developed an ontology and logical language. The resulting formalization involves over 10,000 different research units in a nested treelike structure, 10 levels deep, that relates the 6.6 million biomass measurements to their logical description. This formalization describes how a machine contributed to scientific knowledge. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article “Machines Fall Short of Revolutionary Science,” by P. W. Anderson and E. Abrahams in the June 19, 2009 issue.