Ongoing breakthroughs with CRISPR/Cas-based editing could potentially revolutionize modern medicine, but there are many questions to resolve about the ethical implications for its therapeutic ...application. We conducted a worldwide online survey of over 12,000 people recruited via social media to gauge attitudes toward this technology and discuss our findings here.
Ongoing breakthroughs with CRISPR/Cas-based editing could potentially revolutionize modern medicine, but there are many questions to resolve about the ethical implications for its therapeutic application. We conducted a worldwide online survey of over 12,000 people recruited via social media to gauge attitudes toward this technology and discuss our findings here.
The CRISPR/Cas system could provide an efficient and reliable means of editing the human genome and has the potential to revolutionize modern medicine; however, rapid developments are raising complex ...ethical issues. There has been significant scientific debate regarding the acceptability of some applications of CRISPR/Cas, with leaders in the field highlighting the need for the lay public's views to shape expert discussion. As such, we sought to determine the factors that influence public opinion on gene editing. We created a 17-item online survey translated into 11 languages and advertised worldwide. Topic modeling was used to analyze textual responses to determine what factors influenced respondents' opinions toward human somatic or embryonic gene editing, and how this varied among respondents with differing attitudes and demographic backgrounds. A total of 3,988 free-text responses were analyzed. Respondents had a mean age of 32 (range, 11-90) years, and 37% were female. The most prevalent topics cited were Future Generations, Research, Human Editing, Children, and Health. Respondents who disagreed with gene editing for health-related purposes were more likely to cite the topic Better Understanding than those who agreed to both somatic and embryonic gene editing. Respondents from Western backgrounds more frequently discussed Future Generations, compared with participants from Eastern countries. Religious respondents did not cite the topic Religious Beliefs more frequently than did nonreligious respondents, whereas Christian respondents were more likely to cite the topic Future Generations. Our results suggest that public resistance to human somatic or embryonic gene editing does not stem from an inherent mistrust of genome modification, but rather a desire for greater understanding. Furthermore, we demonstrate that factors influencing public opinion vary greatly amongst demographic groups. It is crucial that the determinants of public attitudes toward CRISPR/Cas be well understood so that the technology does not suffer the negative public sentiment seen with previous genetic biotechnologies.
Predictive gene expression modelling is an important tool in computational biology due to the volume of high-throughput sequencing data generated by recent consortia. However, the scope of previous ...studies has been restricted to a small set of cell-lines or experimental conditions due an inability to leverage distributed processing architectures for large, sharded data-sets.
We present a distributed implementation of gene expression modelling using the MapReduce paradigm and prove that performance improves as a linear function of available processor cores. We then leverage the computational efficiency of this framework to explore the variability of epigenetic function across fifty histone modification data-sets from variety of cancerous and non-cancerous cell-lines.
We demonstrate that the genome-wide relationships between histone modifications and mRNA transcription are lineage, tissue and karyotype-invariant, and that models trained on matched -omics data from non-cancerous cell-lines are able to predict cancerous expression with equivalent genome-wide fidelity.
Characterising programs of gene regulation by studying individual protein-DNA and protein-protein interactions would require a large volume of high-resolution proteomics data, and such data are not ...yet available. Instead, many gene regulatory network (GRN) techniques have been developed, which leverage the wealth of transcriptomic data generated by recent consortia to study indirect, gene-level relationships between transcriptional regulators. Despite the popularity of such methods, previous methods of GRN inference exhibit limitations that we highlight and address through the lens of information theory.
We introduce new model-free and non-linear information theoretic measures for the inference of GRNs and other biological networks from continuous-valued data. Although previous tools have implemented mutual information as a means of inferring pairwise associations, they either introduce statistical bias through discretisation or are limited to modelling undirected relationships. Our approach overcomes both of these limitations, as demonstrated by a substantial improvement in empirical performance for a set of 160 GRNs of varying size and topology.
The information theoretic measures described in this study yield substantial improvements over previous approaches (e.g. ARACNE) and have been implemented in the latest release of NAIL (Network Analysis and Inference Library). However, despite the theoretical and empirical advantages of these new measures, they do not circumvent the fundamental limitation of indeterminacy exhibited across this class of biological networks. These methods have presently found value in computational neurobiology, and will likely gain traction for GRN analysis as the volume and quality of temporal transcriptomics data continues to improve.
Predictive modelling of gene expression provides a powerful framework for exploring the regulatory logic underpinning transcriptional regulation. Recent studies have demonstrated the utility of such ...models in identifying dysregulation of gene and miRNA expression associated with abnormal patterns of transcription factor (TF) binding or nucleosomal histone modifications (HMs). Despite the growing popularity of such approaches, a comparative review of the various modelling algorithms and feature extraction methods is lacking. We define and compare three methods of quantifying pairwise gene-TF/HM interactions and discuss their suitability for integrating the heterogeneous chromatin immunoprecipitation (ChIP)-seq binding patterns exhibited by TFs and HMs. We then construct log-linear and ϵ-support vector regression models from various mouse embryonic stem cell (mESC) and human lymphoblastoid (GM12878) data sets, considering both ChIP-seq- and position weight matrix- (PWM)-derived in silico TF-binding. The two algorithms are evaluated both in terms of their modelling prediction accuracy and ability to identify the established regulatory roles of individual TFs and HMs. Our results demonstrate that TF-binding and HMs are highly predictive of gene expression as measured by mRNA transcript abundance, irrespective of algorithm or cell type selection and considering both ChIP-seq and PWM-derived TF-binding. As we encourage other researchers to explore and develop these results, our framework is implemented using open-source software and made available as a preconfigured bootable virtual environment.
Computer vision plays a major role in most autonomous systems and is particularly fundamental within the robotics industry, where vision data are the main input to all navigation and high-level ...decision making. Although there is significant research into developing and optimising algorithms for feature detection and environment reconstruction, there is a comparative lack of emphasis on how best to map these abstract concepts onto an appropriate software architecture. In this study, we distinguish between functional and non-functional requirements of a computer vision system. Using a RoboCup humanoid robot system as a case study, we propose and develop a software architecture that fulfills the latter criteria. To demonstrate the modifiability of the proposed architecture, we detail a number of examples of feature detection algorithms that were modified to capture the rapidly evolving RoboCup requirements, with emphasis on which aspects of the underlying framework required modification to support their integration. To demonstrate portability, we port our vision system (designed for an application-specific DARwIn-OP humanoid robot) to a general-purpose, Raspberry Pi computer. We evaluate the processing time on both hardware platforms for several image streams under different conditions and compare relative to a vision system optimised for functional requirements only. The architecture and implementation presented in this study provide a highly generalisable framework for computer vision system design that is of particular benefit in research and development, competition and other environments in which rapid system evolution is necessary to adapt to domain-specific requirements.
Within the structural and grammatical bounds of a common language, all authors develop their own distinctive writing styles. Whether the relative occurrence of common words can be measured to produce ...accurate models of authorship is of particular interest. This work introduces a new score that helps to highlight such variations in word occurrence, and is applied to produce models of authorship of a large group of plays from the Shakespearean era.
A text corpus containing 55,055 unique words was generated from 168 plays from the Shakespearean era (16th and 17th centuries) of undisputed authorship. A new score, CM1, is introduced to measure variation patterns based on the frequency of occurrence of each word for the authors John Fletcher, Ben Jonson, Thomas Middleton and William Shakespeare, compared to the rest of the authors in the study (which provides a reference of relative word usage at that time). A total of 50 WEKA methods were applied for Fletcher, Jonson and Middleton, to identify those which were able to produce models yielding over 90% classification accuracy. This ensemble of WEKA methods was then applied to model Shakespearean authorship across all 168 plays, yielding a Matthews' correlation coefficient (MCC) performance of over 90%. Furthermore, the best model yielded an MCC of 99%.
Our results suggest that different authors, while adhering to the structural and grammatical bounds of a common language, develop measurably distinct styles by the tendency to over-utilise or avoid particular common words and phrasings. Considering language and the potential of words as an abstract chaotic system with a high entropy, similarities can be drawn to the Maxwell's Demon thought experiment; authors subconsciously favour or filter certain words, modifying the probability profile in ways that could reflect their individuality and style.
'Reproducible research' has received increasing attention over the past few years as bioinformatics and computational biology methodologies become more complex. Although reproducible research is ...progressing in several valuable ways, we suggest that recent increases in internet bandwidth and disk space, along with the availability of open-source and free-software licences for tools, enable another simple step to make research reproducible. In this article, we urge the creation of minimal virtual reference environments implementing all the tools necessary to reproduce a result, as a standard part of publication. We address potential problems with this approach, and show an example environment from our own work.
Physically realistic simulated environments are powerful platforms for enabling measurable, replicable, and statistically robust investigation of complex robotic systems. Such environments are ...epitomized by the RoboCup (RC) simulation leagues, which have been successfully utilized to conduct massively parallel experiments on a variety of topics, including optimization of bipedal locomotion, self-localization from noisy perception data, and planning complex multiagent strategies without direct agent-to-agent communication. Many of these systems are later transferred to physical robots, making the simulation leagues invaluable beyond the scope of simulated soccer matches.
Transcription factors (TFs) and histone modifications (HMs) play critical roles in gene expression by regulating mRNA transcription. Modelling frameworks have been developed to integrate ...high-throughput omics data, with the aim of elucidating the regulatory logic that results from the interactions of DNA, TFs and HMs. These models have yielded an unexpected and poorly understood result: that TFs and HMs are statistically redundant in explaining mRNA transcript abundance at a genome-wide level.
We constructed predictive models of gene expression by integrating RNA-sequencing, TF and HM chromatin immunoprecipitation sequencing and DNase I hypersensitivity data for two mammalian cell types. All models identified genome-wide statistical redundancy both within and between TFs and HMs, as previously reported. To investigate potential explanations, groups of genes were constructed for ontology-classified biological processes. Predictive models were constructed for each process to explore the distribution of statistical redundancy. We found significant variation in the predictive capacity of TFs and HMs across these processes and demonstrated the predictive power of HMs to be inversely proportional to process enrichment for housekeeping genes.
It is well established that the roles played by TFs and HMs are not functionally redundant. Instead, we attribute the statistical redundancy reported in this and previous genome-wide modelling studies to the heterogeneous distribution of HMs across chromatin domains. Furthermore, we conclude that statistical redundancy between individual TFs can be readily explained by nucleosome-mediated cooperative binding. This could possibly help the cell confer regulatory robustness by rejecting signalling noise and allowing control via multiple pathways.
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