CCP11 group meeting - towards the functional analysis of microarrays

The CCP11 project [2] aims to foster bioinformatics in the UK through conferences, workshops and the provision of Web resources. In March 2002, CCP11 held a meeting in Manchester, UK, on the functional analysis of microarrays. This was part of Manchester BioinformaticsWeek-three consecutive short bioinformatics meetings held in the attractive setting of the Chancellor's Conference Centre at the University of Manchester. The other meetings in the series were a workshop on ontologies and the 12th Annual MASAMB (Mathematical and Statistical Aspects of Molecular Biology) Conference. Many delegates were able to attend more than one meeting, which led to a useful cross-fertilization of ideas across the bioinformatics community. The CCP11 meeting shared with MASAMB a strong emphasis on the statistical analysis and interpretation of data-most often image intensity data.     

From proteins to systems: the British Society for Proteomics Research (BSPR) meeting 2005

This report describes the highlights of the second scientific meeting of the British Society for Proteome Research (BSPR), jointly organised with the European Bioinformatics Institute (EBI), and held at The Genome Centre, Cambridge UK in July 2005. The theme of the meeting was "From Proteins to Systems" covering many diverse aspects of proteomics, bioinformatics and systems biology.     

Twenty years of neurological prosthesis-making

The UK Medical Research Council's Neurological Prosthesis Unit was formed on 1 October 1968. In this review, Peter Donaldson, who has been with the unit from the beginning, reflects on what seem to him to be the most important contributions to implant technology from the unit, and suggests some possible developments for the future.     

BSPR/EBI 2007 meeting report--Integrative Proteomics: From Molecules to Systems. July 25-27, 2007 Wellcome Trust Conference Centre, Hinxton, UK.

This report reviews the joint British Society for Proteome Research (BSPR) and European Bioinformatics Institute (EBI) 2007 meeting, 'Integrative Proteomics: From Molecules to Systems' which took place at the Wellcome Trust Conference Centre, Hinxton, UK, from 25th to 27th July. The aim of this year's meeting was to explore how the integration of 'omic' technologies can lead to a comprehensive understanding of cellular organization, differentiation and signalling. Studies investigating protein-protein interactions and trafficking illustrated how the combination of proteomics and bioinformatics is allowing systems biology to develop as a discipline in its own right.     

Peak drug levels in linear pharmacokinetic systems—II. Conditions for a paradoxical injection rate effect with rectangular input

The preceding paper (Thorn, 1981) has shown that in a linear pharmacokinetic system with a multimodal impulse response the peak drug level may sometimes be smaller with slower rates of injection. This paper presents two theorems on this paradoxical injection rate effect where the injection is a constant infusion of finite duration. The first theorem establishes a graphical method for determining whether a given impulse response will give a paradoxical injection rate effect; and the second establishes that the maximum paradoxical increase in peak drug level is by a factor of two. It is further shown that in order to approach this maximum paradoxical increase the impulse response must contain two isolated, sharp, narrow pulses of approximately equal area. Some examples of bimodal arterial dye-dilution curves from the literature are discussed as impulse responses; and there is also a discussion of the behavior of drug level maxima and minima at different injection rates. This work was supported in part by U.S. Public Health Service Research Grant GM 21269 from the National Institute of General Medical Sciences, and in part by Biomedical Research Support Grant S07 RR 05932 from the National Institutes of Health. A portion of this work was presented at the Annual Meeting of the Society for Mathematical Biology at the Medical School of the University of Pennsylvania, Philadelphia, August 1976.     

Recent developments in the monitoring,modeling and control of biological production systems

Current trends in the development of methods for monitoring, modeling and controlling biological production systems are reviewed from a bioengineering perspective. The ability to measure intracellular conditions in bioprocesses using genomics and other bioinformatics tools is addressed. Devices provided via micromachining techniques and new real-time optical technology are other novel methods that may facilitate biosystem engineering. Mathematical modeling of data obtained from bioinformatics or real-time monitoring methods are necessary in order to handle the dense flows of data that are generated. Furthermore, control methods must be able to cope with these data flows in efficient ways that can be implemented in plant-wide computer communication systems.Mini-review for the proceedings of the M3C conference     

USDA Stakeholder Workshop on Animal Bioinformatics: Summary and Recommendations

An electronic workshop was conducted on 4 November-13 December 2002 to discuss current issues and needs in animal bioinformatics. The electronic (e-mail listserver) format was chosen to provide a relatively speedy process that is broad in scope, cost-efficient and easily accessible to all participants. Approximately 40 panelists with diverse species and discipline expertise communicated through the panel e-mail listserver. The panel included scientists from academia, industry and government, in the USA, Australia and the UK. A second 'stakeholder' e-mail listserver was used to obtain input from a broad audience with general interests in animal genomics. The objectives of the electronic workshop were: (a) to define priorities for animal genome database development; and (b) to recommend ways in which the USDA could provide leadership in the area of animal genome database development. E-mail messages from panelists and stakeholders are archived at http://genome.cvm.umn.edu/bioinfo/. Priorities defined for animal genome database development included: (a) data repository; (b) tools for genome analysis; (c) annotation; (d) practical application of genomic data; and (e) a biological framework for DNA sequence. A stable source of funding, such as the USDA Agricultural Research Service (ARS), was recommended to support maintenance of data repositories and data curation. Continued support for competitive grants programs within the USDA Cooperative State Research, Education and Extension Service (CSREES) was recommended for tool development and hypothesis-driven research projects in genome analysis. Additional stakeholder input will be required to continuously refine priorities and maximize the use of limited resources for animal bioinformatics within the USDA.     

A review of bioinformatics education in the UK

If the completion of the first draft of the human genome represents the coming of age of bioinformatics, then the emergence of bioinformatics as a university degree subject represents its establishment. In this paper bioinformatics as a subject for formal study is discussed, rather than as a subject for research, and a selection of the taught, mainly graduate, courses currently available in the UK are reviewed. Throughout, the author tries to draw parallels between the integration of bioinformatics into biomedical research and teaching today, and that of molecular biology, two decades ago. Others have made this analogy between these two relatively young disciplines. Although research sources are referenced, the author makes no pretence of objectivity. This article contains his opinions, and those of a number of current bioinformatics course organisers whose comments on the subject were solicited in advance specifically for this paper. The course organisers kindly advised how they planned their curricula, and described the special strengths of their programmes. Comments from present and former students of several bioinformatics degree programmes were also solicited. Except where individuals are directly quoted, any opinions expressed herein should be considered the author's. Compared with its sister piece [Marion Zatz, in previous issue of Briefings in Bioinformatics pp. 353], this paper is less about funding policy--which, in the UK, has lately (if belatedly) been more generous towards bioinformatics teaching--than it is about practice and content; the requirements of the bioinformatics research communities, the corresponding emphases of bioinformatics courses, and the general market for holders of bioinformatics degrees. Individual courses are cited throughout as examples, but the final section contains a full annotated listing with URL addresses. Based on the author's own experience of practising and teaching bioinformatics, he describes the skills he believes will be most useful to bioinformaticians in the near future and suggests ways to prepare students of bioinformatics for a fall in demand for those abilities.     

Peak drug levels in linear pharmacokinetic systems—I. Effect of rate of injection

This paper presents three theorems on the peak drug levels that result from injection into a linear pharmacokinetic system. As a preliminary, the “rate of injection” is defined in terms of time expansion or time contraction of the injection function (input). The first theorem then states that the peak drug level will not be greater when the rate of injection is slow than when it is fast, if the impulse response is unimodal. The second theorem sets limits for the time of the maximum drug level, in relation to the time of the maximum of the (unimodal) impulse response and the duration of the input. The third theorem defines conditions which assure a definitely lower peak drug level if the rate of injection is slower. A graphical method is suggested for determining the times and magnitudes of the peak drug levels that result from constant infusions of a fixed dose at different rates. An example is provided to show that if the impulse response is multimodal then the peak drug level may sometimes increase with a decrease in the injection rate. Supported in part by U.S. Public Health Service Research Grant GM 21269 from the National Institute of General Medical Sciences, and in part by Biomedical Research Support Grant S07 RR 05392 from the National Institutes of Health. A portion of this work was presented at the Annual Meeting of the Society for Mathematical Biology at the Medical School of the University of Pennsylvania, Philadelphia, August 1976.     

Designing research funding schemes to promote global health equity: An exploration of current practice in health systems research

International research is an essential means of reducing health disparities between and within countries and should do so as a matter of global justice. Research funders from high‐income countries have an obligation of justice to support health research in low and middle‐income countries (LMICs) that furthers such objectives. This paper investigates how their current funding schemes are designed to incentivise health systems research in LMICs that promotes health equity. Semi‐structured in‐depth interviews were performed with 16 grants officers working for 11 funders and organisations that support health systems research: the Alliance for Health Policy and Systems Research, Comic Relief, Doris Duke Foundation, European Commission, International Development Research Centre, Norwegian Agency for Development Cooperation, Research Council of Norway, Rockefeller Foundation, UK Department of International Development, UK Medical Research Council, and Wellcome Trust. Thematic analysis of the data demonstrates their funding schemes promote health systems research with (up to) five key features that advance health equity: being conducted with worst‐off populations, focusing on research topics that advance equitable health systems, having LMIC ownership of the research agenda, strengthening LMIC research capacity, and having an impact on health disparities. The different types of incentives that encouraged proposed projects to have these features are identified and classified by their strength (strong, moderate, weak). It is suggested that research funders ought to create and maintain funding schemes with strong incentives for the features identified above in order to more effectively help reduce global health disparities.     

蛋白质相互作用的生物信息学研究进展

生命过程的分子基础在于生物分子之间的相互作用,其中蛋白质分子之间的相互作用占有极其重要的地位。研究蛋白质相互作用对于理解生命的真谛、探讨致病微生物的致病机理,以及研究新药提高人们的健康水平具有重要的作用。用生物信息学的方法研究蛋白质的相互作用已经取得了许多重要的成果,但也有很多问题还需解决。本文从蛋白质相互作用的数据库、预测方法、可预测蛋白质相互作用的网上服务、蛋白质相互作用网络等几方面,对蛋白质相互作用的生物信息学研究成果及其存在的问题做了概述。     

Study of cutaneous nociception by means of chemical agents

The response was investigated of cutaneous C-fiber polymodal mechano-thermo-sensitive sensory units (SMT units) to injecting potassium, acetylcholine, and methacholine ions at noxious and subnoxious concentrations into the arteries of anesthetized cats. Subnoxious chemical stimulation induced low-frequency excitation in SMT units. The parameters of firing in these units, when subjected to excitation during noxious or subnoxious chemical stimulation, may be used to estimate the analgesic action of local anesthetics. Local anesthesia may be achieved by inhibiting exclusively high-frequency discharge in SMT units, without complete blockade of these sensors. We propose use-dependent neural excitation blockers for this purpose. SMT units were found to be inhibited in this way by mechanical stimulation under the action of lidocaine or n-propylaj-maline. Mathematical modeling of C-fibers showed that slow alterations in ionic permeability play a major part in determining firing rate produced by chemical stimulation.Experimental Cardiological Research Institute, All-Union Cardiological Research Center, Russian Academy of Medical Sciences, Moscow. Translated from Neirofiziologiya, Vol. 24, No. 5, pp. 517–529, September–October, 1992.     

The UK Human Genome Mapping Project online computing service

This paper presents an overview of computing and networkingfacilities developed by the Medical Research Council to provideonline computing support to the Human Genome Mapping Project(HGMP) in the UK. The facility is connected to a number of othercomputing facilities in various centres of genetics and molecularbiology research excellence, either directly via high-speedlinks or through national and international wide–areanetworks. The paper describes the design and implementationof the current system, a ‘client/server’ networkof Sun, IBM, DEC and Apple servers, gateways and workstations.A short outline of online computing services currently deliveredby this system to the UK human genetics research community isalso provided. More information about the services and theiravailability could be obtained by a direct approach to the UKHGMP-RC.     

Book Reviews

McCONWAY, K. J., JONES, M. C., and TAYLOR, P. C. Statistical Modelling using Genstat. SCHINAZI, R. B. Classical and Spatial Point Processes. PERRY, J. E., SMITH, R. H., WOIWOD, I. P., and MORSE, D. R. (editors). Chaos in Real Data: The Analysis of Non‐linear Dynamics from Short Ecological Time Series. BURTON, R. F. Physiology by Numbers, 2nd edition. BERLINER, L. M., NYCHKA, D., and HOAR, T. (editors). Studies in the Atmospheric Sciences. PRAKASA RAO, B. L. S. Statistical Inference for Diffusion Type Processes. DONNER, A. and KLAR, N. Design and Analysis of Cluster Randomization Trials in Health Research. MATIS, J. H. and KIFFE, T. R. Stochastic Population Models: A Compartmental Perspective. LINDSEY, J. K. Models for Repeated Measurements, 2nd edition. FORD, E. D. Scientific Method for Ecological Research. BURNHAM, K. P. and ANDERSON, D. R. Model Selection and Inference: A Practical Information‐Theoretic Approach. COX, D. R. and REID, N. The Theory of the Design of Experiments. PINHEIRO, J. C. and BATES, D. M. Mixed‐effects models in S and S‐PLUS. VENABLES, W. N. and RIPLEY, B. D. S Programming. KRAUSE, A. and OLSON, M. The Basics of S and S‐PLUS. CHEN, M.‐H., SHAO, Q.‐M., and IBRAHIM, J. G. Monte Carlo Methods in Bayesian Computation. SAHAI, H. and AGEEL, M. L. The Analysis of Variance: Fixed, Random, and Mixed Models. EVERITT, B. S. and DUNN, G. Statistical Analysis of Medical Data: New Developments. MUKHOPADHYAY, N. Probability and Statistical Inference. KNIGHT, K. Mathematical Statistics. Brief reports by the editor MILLER, R. E. Optimization: Foundations and Applications. BLAND, M. An Introduction to Medical Statistics, 3rd edition. RABE‐HESKETH, S. and EVERITT, B. A Handbook of Statistical Analyses using Stata, 2nd edition. KOO, J. O. (editor). American Series in Mathematical and Management Sciences Volume 42. Modern Mathematical, Management, and Statistical Sciences, The Index to the 20th Century, Prologue to the 21st Century. MISHRA, S. N. and SHARMA, B. D. (editors). American Series in Mathematical and Management Sciences Volume 43. FIM‐I, Forum for Interdisciplinary Mathematics Proceedings on Statistical Inference, Combinatorics and Related Areas, Volume I of Proceedings of Banaras Hindu University (BHU) Conference (Varanasi, India, December 1997). VENABLES, W. N. and RIPLEY, B. D. Modern Applied Statistics with S‐PLUS, 3rd edition.     

The stabilisation of a transient mutagen-sensitive state in Neurospora by the protein synthesis inhibitor actidione

Summary Experimental evidence has been obtained to show that a transient mutagen sensitive state, believed to be induced in Neurospora by DEB, can be stabilised by the protein synthesis inhibitor actidione. Sensitisation can thus be separated from the complicating effects of traces of the DEB retained by the cells following washing. The bearing of these results on the interpretation of the DEB after-effect and DEB mutation induction curves is briefly discussed.Research supported by the Medical Research Council.     

Applied problems of mathematical biology and bioinformatics

Mathematical biology and bioinformatics represent a new and rapidly progressing line of investigations which emerged in the course of work on the project “Human Genome”. The main applied problems of these sciences are drug design, patient-specific medicine and nanobioelectronics. It is shown that progress in the technology of mass sequencing of the human genome has set the stage for starting the national program on patient-specific medicine.     

G蛋白偶联受体计算研究的进展和前瞻

G蛋白偶联受体(G protein-coupled receptor,GPCR)是含有七个跨膜螺旋的一类重要蛋白,是迄今为止发现的最大的多药物靶标受体超蛋白家族。例如,目前上市药物中有超过30%是以GPCR为靶点的。然而,与GPCR重要性形成强烈反差的是科学界对于其结构与功能的了解非常贫乏,主要原因是通过实验手段来获得GPCR的结构与功能信息极其困难。利用生物信息学方法从基因组规模的数据中识别GPCR并预测三维结构是可行途径之一。基于生物信息学的GPCR研究将为新型药物靶标的筛选和药物的开发提供一定的帮助。本文论述了几种较为典型的GPCR计算方法,并基于已有研究提出可能的创新性研究策略来解决GPCR蛋白识别、跨膜区定位、以及结构和功能预测等问题。