Lonnie R. Welch

AGRIS: the Arabidopsis Gene Regulatory Information Server, an update

The Arabidopsis Gene Regulatory Information Server (AGRIS; http://arabidopsis.med.ohio-state.edu/) provides a comprehensive resource for gene regulatory studies in the model plant Arabidopsis thaliana. Three interlinked databases, AtTFDB, AtcisDB and AtRegNet, furnish comprehensive and updated information on transcription factors (TFs), predicted and experimentally verified cis-regulatory elements (CREs) and their interactions, respectively. In addition to significant contributions in the identification of the entire set of TF–DNA interactions, which are the key to understand the gene regulatory networks that govern Arabidopsis gene expression, tools recently incorporated into AGRIS include the complete set of words length 5–15 present in the Arabidopsis genome and the integration of AtRegNet with visualization tools, such as the recently developed ReIN application. All the information in AGRIS is publicly available and downloadable upon registration.

A Bioinformatics Approach to the Identification, Classification, and Analysis of Hydroxyproline-Rich Glycoproteins

Hydroxyproline-rich glycoproteins (HRGPs) are a superfamily of plant cell wall proteins that function in diverse aspects of plant growth and development. This superfamily consists of three members: hyperglycosylated arabinogalactan proteins (AGPs), moderately glycosylated extensins (EXTs), and lightly glycosylated proline-rich proteins (PRPs). Hybrid and chimeric versions of HRGP molecules also exist. In order to “mine” genomic databases for HRGPs and to facilitate and guide research in the field, the BIO OHIO software program was developed that identifies and classifies AGPs, EXTs, PRPs, hybrid HRGPs, and chimeric HRGPs from proteins predicted from DNA sequence data. This bioinformatics program is based on searching for biased amino acid compositions and for particular protein motifs associated with known HRGPs. HRGPs identified by the program are subsequently analyzed to elucidate the following: (1) repeating amino acid sequences, (2) signal peptide and glycosylphosphatidylinositol lipid anchor addition sequences, (3) similar HRGPs via Basic Local Alignment Search Tool, (4) expression patterns of their genes, (5) other HRGPs, glycosyl transferase, prolyl 4-hydroxylase, and peroxidase genes coexpressed with their genes, and (6) gene structure and whether genetic mutants exist in their genes. The program was used to identify and classify 166 HRGPs from Arabidopsis (Arabidopsis thaliana) as follows: 85 AGPs (including classical AGPs, lysine-rich AGPs, arabinogalactan peptides, fasciclin-like AGPs, plastocyanin AGPs, and other chimeric AGPs), 59 EXTs (including SP5 EXTs, SP5/SP4 EXTs, SP4 EXTs, SP4/SP3 EXTs, a SP3 EXT, “short” EXTs, leucine-rich repeat-EXTs, proline-rich extensin-like receptor kinases, and other chimeric EXTs), 18 PRPs (including PRPs and chimeric PRPs), and AGP/EXT hybrid HRGPs.

Specification and modeling of dynamic, distributed real-time systems

Time constrained systems which operate in dynamic environments may have unknown worst case scenarios, may have large variances in the sizes of the data and event sets that they process (and thus, have large variances in execution latencies and resource requirements), and may not be statically characterizable, even by time invariant statistical distributions. The paper presents a specification language for describing environment dependent features. Also presented is an abstract model that is constructed (statically) from the specifications, and is augmented (dynamically,) with the state of environment dependent features. The model is used to define techniques for QoS (quality of service) monitoring, QoS diagnosis, and resource allocation analysis. Experimental results show the effectiveness of the approach for specification of real time QoS, detection and diagnosis of QoS failures, and restoration of acceptable QoS via reallocation of distributed computer and network resources.

DeSiDeRaTa: QoS Management Technology for Dynamic, Scalable, Dependable, Real-Time Systems

Abstract The DeSiDeRaTa project is producing technology to enable the engineering of the emerging generation of distributed real-time systems. Such systems have rigorous Quality of Service (QoS) objectives. They must behave in a dependable manner, respond to threats in a timely fashion and provide continuous availability, even within hostile and unknown environments. To provide the desired QoS in such a context, the DeSiDeRaTa project focuses on QoS specification, dynamic QoS management middleware, and benchmarking of dynamic real-time systems. This paper discusses each of these aspects, and presents experimental results of applying DeSiDeRaTa technology to a dynamic realtime benchmark system.

Word-based characterization of promoters involved in human DNA repair pathways

BackgroundDNA repair genes provide an important contribution towards the surveillance and repair of DNA damage. These genes produce a large network of interacting proteins whose mRNA expression is likely to be regulated by similar regulatory factors. Full characterization of promoters of DNA repair genes and the similarities among them will more fully elucidate the regulatory networks that activate or inhibit their expression. To address this goal, the authors introduce a technique to find regulatory genomic signatures, which represents a specific application of the genomic signature methodology to classify DNA sequences as putative functional elements within a single organism.ResultsThe effectiveness of the regulatory genomic signatures is demonstrated via analysis of promoter sequences for genes in DNA repair pathways of humans. The promoters are divided into two classes, the bidirectional promoters and the unidirectional promoters, and distinct genomic signatures are calculated for each class. The genomic signatures include statistically overrepresented words, word clusters, and co-occurring words. The robustness of this method is confirmed by the ability to identify sequences that exist as motifs in TRANSFAC and JASPAR databases, and in overlap with verified binding sites in this set of promoter regions.ConclusionThe word-based signatures are shown to be effective by finding occurrences of known regulatory sites. Moreover, the signatures of the bidirectional and unidirectional promoters of human DNA repair pathways are clearly distinct, exhibiting virtually no overlap. In addition to providing an effective characterization method for related DNA sequences, the signatures elucidate putative regulatory aspects of DNA repair pathways, which are notably under-characterized.

Bioinformatics Curriculum Guidelines: Toward a Definition of Core Competencies

Rapid advances in the life sciences and in related information technologies necessitate the ongoing refinement of bioinformatics educational programs in order to maintain their relevance. As the discipline of bioinformatics and computational biology expands and matures, it is important to characterize the elements that contribute to the success of professionals in this field. These individuals work in a wide variety of settings, including bioinformatics core facilities, biological and medical research laboratories, software development organizations, pharmaceutical and instrument development companies, and institutions that provide education, service, and training. In response to this need, the Curriculum Task Force of the International Society for Computational Biology (ISCB) Education Committee seeks to define curricular guidelines for those who train and educate bioinformaticians. The previous report of the task force summarized a survey that was conducted to gather input regarding the skill set needed by bioinformaticians [1]. The current article details a subsequent effort, wherein the task force broadened its perspectives by examining bioinformatics career opportunities, surveying directors of bioinformatics core facilities, and reviewing bioinformatics education programs. The bioinformatics literature provides valuable perspectives on bioinformatics education by defining skill sets needed by bioinformaticians, presenting approaches for providing informatics training to biologists, and discussing the roles of bioinformatics core facilities in training and education. The skill sets required for success in the field of bioinformatics are considered by several authors: Altman [2] defines five broad areas of competency and lists key technologies; Ranganathan [3] presents highlights from the Workshops on Education in Bioinformatics, discussing challenges and possible solutions; Yales interdepartmental PhD program in computational biology and bioinformatics is described in [4], which lists the general areas of knowledge of bioinformatics; in a related article, a graduate of Yales PhD program reflects on the skills needed by a bioinformatician [5]; Altman and Klein [6] describe the Stanford Biomedical Informatics (BMI) Training Program, presenting observed trends among BMI students; the American Medical Informatics Association defines competencies in the related field of biomedical informatics in [7]; and the approaches used in several German universities to implement bioinformatics education are described in [8]. Several approaches to providing bioinformatics training for biologists are described in the literature. Tan et al. [9] report on workshops conducted to identify a minimum skill set for biologists to be able to address the informatics challenges of the “-omics” era. They define a requisite skill set by analyzing responses to questions about the knowledge, skills, and abilities that biologists should possess. The authors in [10] present examples of strategies and methods for incorporating bioinformatics content into undergraduate life sciences curricula. Pevzner and Shamir [11] propose that undergraduate biology curricula should contain an additional course, “Algorithmic, Mathematical, and Statistical Concepts in Biology.” Wingren and Botstein [12] present a graduate course in quantitative biology that is based on original, pathbreaking papers in diverse areas of biology. Johnson and Friedman [13] evaluate the effectiveness of incorporating biological informatics into a clinical informatics program. The results reported are based on interviews of four students and informal assessments of bioinformatics faculty. The challenges and opportunities relevant to training and education in the context of bioinformatics core facilities are discussed by Lewitter et al. [14]. Relatedly, Lewitter and Rebhan [15] provide guidance regarding the role of a bioinformatics core facility in hiring biologists and in furthering their education in bioinformatics. Richter and Sexton [16] describe a need for highly trained bioinformaticians in core facilities and provide a list of requisite skills. Similarly, Kallioniemi et al. [17] highlight the roles of bioinformatics core units in education and training. This manuscript expands the body of knowledge pertaining to bioinformatics curriculum guidelines by presenting the results from a broad set of surveys (of core facility directors, of career opportunities, and of existing curricula). Although there is some overlap in the findings of the surveys, they are reported separately, in order to avoid masking the unique aspects of each of the perspectives and to demonstrate that the same themes arise, even when different perspectives are considered. The authors derive from their surveys an initial set of core competencies and relate the competencies to three different categories of professions that have a need for bioinformatics training.

Resource Management Middleware for Dynamic, DependableReal-Time Systems

Thispaper presents resource management techniques that achieve thequality of service (QoS) requirements of dynamic real-time systemsusing open architectures and commercial off-the-shelf technologies(COTS). Dynamic real-time systems are subject to constant changessuch as a varying external environment, overload of internalsystems, component failure, and evolving operational requirements.Examples of such systems include the emerging generation of computer-based,command and control systems of the U.S. Navy. To enable the engineeringof such systems, we present adaptive resource management middlewaretechniques that achieve the QoS requirements of the system. Themiddleware performs QoS monitoring and failure detection, QoSdiagnosis, and reallocation of resources to adapt the systemto achieve acceptable levels of QoS. Experimental characterizationsof the middleware using a real-time benchmark illustrate itseffectiveness for adapting the system for achieving the desiredreal-time and survivability QoS during overload situations.

ON SPECIFICATION OF REUSABLE SOFTWARE COMPONENTS

For widespread reuse in a component-based software industry, a component must be designed and developed to be reused. Benefits of reuse are maximized when a component is reused “as is” (possibly with provisions for expected customization, such as through parameters), based only on its specification. The expression of the specification of a component is crucial in this setting. The specification must be formal, yet understandable, as well as abstract and implementation-independent. The specification also must make it possible to demonstrate correctness of an implementation of the specification and permit formal reasoning about its behavior in a client program. This paper explains how it is possible to write specifications with these properties in RESOLVE, a conceptual framework that we have developed for constructing reusable software components.

A model for scheduling of object-based, distributed real-time systems

This paper describes a general model for pre-run-time scheduling of distributed real-time systems that are composed of abstract data types (definable in languages such as Ada, Clu and Modula-2) and abstract data objects (which can be defined in C++, Eiffel and RT Euclid). An architecture model, a programming paradigm, and execution and communication paradigms form the basis for this general model. The model includesabsolute timing constraints to represent periodicity and deadlines,relative timing constraints to model several kinds of timed precedence relations and synchronization requirements,independency constraints to capture non-determinism of conditionals and repetitions, andconsistency constraints to enforce consistent use of resources. In this paper, the model is formalized to obtain a mathematical foundation on which assignment (Verhoosel et al. 1993a, Welch 1992, Welch et al. 1993) and pre-run-time scheduling problems (Verhoosel et al. 1991, Verhoosel 1992, 1993a, 1993c) are defined. Additionally, the model is extended to allow exploitation of parallelism from programs, a technique that can be used during assignment and scheduling for meeting timing constraints.

Heterogeneous resource management for dynamic real-time systems

Dynamic real-time systems face many resource management problems. This paper addresses the following problems: (1) dynamic resource allocation to provide QoS objectives, (2) heterogeneous resources, and (3) non-intrusive accurate monitoring of QoS, resource availability and resource needs. This paper describes the techniques of a resource manager handling the above problems to support the QoS of dynamic distributed real-time systems. The contributions of this paper to solve these problems are as follows: unification of dynamic resource requirements among heterogeneous hosts, control of resources in heterogeneous environments, feasibility analysis and dynamic load balancing/sharing. Our heuristic allocation scheme not only allows higher workloads than the random, round-robin and least-load schemes by 257%, 142% and 36.4%, respectively, but it also improves the QoS compared to those schemes by 38.6%, 28.5% and 31.6%, respectively.