相关论文
2009 - 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Modeling current pathways for therapeutic electrical applications

In determining how various devices will provide therapeutic currents it is necessary to know the current pathways along with the current densities and voltage gradients in the tissues of interest and in other tissues that may be influenced. In order to obtain this information a high resolution, computer based model (3.8 million elements) was created using gated ECG MRI images from an adult male. The model used the finite difference approach to obtain the needed data. A user friendly, graphical interface was developed for a PC program. The features of the program along with examples from studying the electrical therapies of pacing and defibrillation will be given. It will be show that the conductivity of the entire thorax is important in determining the current pathways within the heart.

2005 - Plant, cell & environment
Intrinsic and environmental response pathways that regulate root system architecture.

Root system development is an important agronomic trait. The right architecture in a given environment allows plants to survive periods of water of nutrient deficit, and compete effectively for resources. Root systems also provide an optimal system for studying developmental plasticity, a characteristic feature of plant growth. This review proposes a framework for describing the pathways regulating the development of complex structures such as root systems: intrinsic pathways determine the characteristic architecture of the root system in a given plant species, and define the limits for plasticity in that species. Response pathways co-ordinate environmental cues with development by modulating intrinsic pathways. The current literature describing the regulation of root system development is summarized here within this framework. Regulatory pathways are also organized based on their specific developmental effect in the root system. All the pathways affect lateral root formation, but some specifically target initiation of the lateral root, while others target the development and activation of the lateral root primordium, or the elongation of the lateral root. Finally, we discuss emerging approaches for understanding the regulation of root system architecture.

2007 - Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques
Metabolic control analysis to identify optimal drug targets.

This chapter describes the basic principles of Metabolic Control Analysis (MCA) which is a quantitative methodology to evaluate the importance and relative contribution of individual metabolic steps in the overall functioning of a particular system. The control on the flux through a metabolic pathway or subsystem can be quantified by the control coefficients of the individual enzymes or components which reflects the extent to which the component is rate-limiting. The perturbation of an individual step is measured by its elasticity coefficient. The effect of perturbation of a single step on the entire pathway or subsystem is, in turn, measured by the response coefficient. Differential control analysis can be used to compare flux through a single metabolic pathway in a pathogen with the same pathway in its host to identify uniquely vulnerable steps with the greatest potential for specifically inhibiting flux through the pathogen metabolic pathway. The utility of this methodology is illustrated with the glycolysis in Trypanosomes and with oncogenic signaling.

2009
Assessment of Theses - A Comparison of Current Approaches Practiced in Engineering Education

To evaluate a student’s work best possible, the assessment of theses written as part of the curriculum has to meet certain standards from both an academic and an industrial perspective to fully embrace the goals of engineering education. Most universities use standardized sets of criteria to assess theses. For the purpose of this research, available assessment forms within the Berliner Kreis, the German-speaking network of institutions active in design education and research, were collected, compared and interpreted to find common evaluation criteria and to judge the current state of how theses in design education are evaluated. This paper describes the theoretical background of evaluating engineering theses, it presents the results of this comprehensive study about current German and international evaluation procedures and criteria, and it concludes on future directions for the evaluation of theses in university education. In summary, 5 to 18 criteria are commonly applied. Based on an initial marking of each criterion, the final assessment is made using an automated suggestion (mostly using spreadsheet applications). Additionally, many institutions do not simply grade the resulting documentation of a project, but they include the active integration of the student into the project as well as presentation and other skills.

2014 - PLoS ONE
Involvement of the GABAergic Septo-Hippocampal Pathway in Brain Stimulation Reward

The hippocampus is a structure related to several cognitive processes, but not very much is known about its putative involvement in positive reinforcement. In its turn, the septum has been related to instrumental brain stimulation reward (BSR) by its electrical stimulation with trains of pulses. Although the anatomical relationships of the septo-hippocampal pathway are well established, the functional relationship between these structures during rewarding behaviors remains poorly understood. To explore hippocampal mechanisms involved in BSR, CA3-evoked field excitatory and inhibitory postsynaptic potentials (fEPSPs, fIPSPs) were recorded in the CA1 area during BSR in alert behaving mice. The synaptic efficiency was determined from changes in fEPSP and fIPSP amplitudes across the learning of a BSR task. The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs. Additionally, we evaluated CA1 local field potentials (LFPs) during a preference task, comparing 8-, 20-, and 100-Hz trains of septal BSR. We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma. These results were replicated by intrahippocampal injections of a GABAB antagonist. Thus, the GABAergic septo-hippocampal pathway seems to carry information involved in the encoding of reward properties, where GABAB receptors seem to play a key role. With regard to the dorsal hippocampus, fEPSPs evoked at the CA3-CA1 synapse seem to reflect the BSR learning process, while hippocampal rhythmic activities are more related to reward properties.

2005 - Critical pathways in cardiology
Acute coronary syndrome critical pathway: chest PAIN caremap: a qualitative research study--provider-level intervention.

Recently published data on healthcare performance continue to show a substantial gap between evidence-based guidelines and management of patients in real-world settings. This article describes an operational model that will be used to test whether a critical pathway applied in a secondary care-level institution may improve the process of care related to acute coronary syndromes (ACS). We have developed the pathway for management of all patients who present to our emergency department with a chief complaint of acute chest pain. Based on individual immediate ischemic event risk, patients are categorized according to a prespecified algorithm under the acronym of "PAIN" (P-Priority risk, A-Advanced risk, I-Intermediate risk, and N-Negative/low risk) as prespecified in an algorithm. Along with the algorithm come 2 detailed order sets, 1 for ST-elevation ACS and another for non ST-elevation ACS. The pathway, together with the 2 order sets, are color-coded with the "PAIN" acronym (P-red, A-yellow, I-yellow, N-green) that will guide patient management according to his or her risk stratification. These colors, similar to the road traffic light code, have been chosen as an easy reference for the provider about the sequential risk level of patients with ACS. This experimental model intends, with its unique structured approach, to increase awareness and improve adherence to the published American Heart Association/American College of Cardiology guidelines for the management of ACS.

2019 - Advances in Game-Based Learning
Game-Based Assessment: The Past Ten Years and Moving Forward

The implementation of assessment features into game-based learning environments is only in its early stages because it adds a very time-consuming step to the design process. The impact on learning and questions toward reliability and validity of technology-based assessment systems are still being questioned. To answer the question of what people are learning from playing games, researchers have been using a variety of methods including external measures, log data capturing in-game actions, and game-related actions beyond the game context. This chapter seeks to identify why research on game-based assessment is still in its infancy, what advances have been achieved over the past 10 years, and which challenges lie ahead for advancing assessment in game-based learning.

2015 - Frontiers in Bioengineering and Biotechnology
A Sense of Balance: Experimental Investigation and Modeling of a Malonyl-CoA Sensor in Escherichia coli

Production of value-added chemicals in microorganisms is regarded as a viable alternative to chemical synthesis. In the past decade, several engineered pathways producing such chemicals, including plant secondary metabolites in microorganisms have been reported; upscaling their production yields, however, was often challenging. Here, we analyze a modular device designed for sensing malonyl-CoA, a common precursor for both fatty acid and flavonoid biosynthesis. The sensor can be used either for high-throughput pathway screening in synthetic biology applications or for introducing a feedback circuit to regulate production of the desired chemical. Here, we used the sensor to compare the performance of several predicted malonyl-CoA-producing pathways, and validated the utility of malonyl-CoA reductase and malonate-CoA transferase for malonyl-CoA biosynthesis. We generated a second-order dynamic linear model describing the relation of the fluorescence generated by the sensor to the biomass of the host cell representing a filter/amplifier with a gain that correlates with the level of induction. We found the time constants describing filter dynamics to be independent of the level of induction but distinctively clustered for each of the production pathways, indicating the robustness of the sensor. Moreover, by monitoring the effect of the copy-number of the production plasmid on the dose–response curve of the sensor, we managed to coarse-tune the level of pathway expression to maximize malonyl-CoA synthesis. In addition, we provide an example of the sensor’s use in analyzing the effect of inducer or substrate concentrations on production levels. The rational development of models describing sensors, supplemented with the power of high-throughput optimization provide a promising potential for engineering feedback loops regulating enzyme levels to maximize productivity yields of synthetic metabolic pathways.

2014 - International Journal of Evolutionary Biology
Mycobacterium tuberculosis H37Rv: In Silico Drug Targets Identification by Metabolic Pathways Analysis

Mycobacterium tuberculosis (Mtb) is a pathogenic bacteria species in the genus Mycobacterium and the causative agent of most cases of tuberculosis. Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. This antibiotic resistance strain lead to development of the new antibiotics or drug molecules which can kill or suppress the growth of Mycobacterium tuberculosis. We have performed an in silico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen Mycobacterium tuberculosis (H37Rv). Novel efforts in developing drugs that target the intracellular metabolism of M. tuberculosis often focus on metabolic pathways that are specific to M. tuberculosis. We have identified five unique pathways for Mycobacterium tuberculosis having a number of 60 enzymes, which are nonhomologous to Homo sapiens protein sequences, and among them there were 55 enzymes, which are nonhomologous to Homo sapiens protein sequences. These enzymes were also found to be essential for survival of the Mycobacterium tuberculosis according to the DEG database. Further, the functional analysis using Uniprot showed involvement of all the unique enzymes in the different cellular components.

2019 - PLoS Computational Biology
Executable pathway analysis using ensemble discrete-state modeling for large-scale data

Pathway analysis is widely used to gain mechanistic insights from high-throughput omics data. However, most existing methods do not consider signal integration represented by pathway topology, resulting in enrichment of convergent pathways when downstream genes are modulated. Incorporation of signal flow and integration in pathway analysis could rank the pathways based on modulation in key regulatory genes. This implementation can be facilitated for large-scale data by discrete state network modeling due to simplicity in parameterization. Here, we model cellular heterogeneity using discrete state dynamics and measure pathway activities in cross-sectional data. We introduce a new algorithm, Boolean Omics Network Invariant-Time Analysis (BONITA), for signal propagation, signal integration, and pathway analysis. Our signal propagation approach models heterogeneity in transcriptomic data as arising from intercellular heterogeneity rather than intracellular stochasticity, and propagates binary signals repeatedly across networks. Logic rules defining signal integration are inferred by genetic algorithm and are refined by local search. The rules determine the impact of each node in a pathway, which is used to score the probability of the pathway’s modulation by chance. We have comprehensively tested BONITA for application to transcriptomics data from translational studies. Comparison with state-of-the-art pathway analysis methods shows that BONITA has higher sensitivity at lower levels of source node modulation and similar sensitivity at higher levels of source node modulation. Application of BONITA pathway analysis to previously validated RNA-sequencing studies identifies additional relevant pathways in in-vitro human cell line experiments and in-vivo infant studies. Additionally, BONITA successfully detected modulation of disease specific pathways when comparing relevant RNA-sequencing data with healthy controls. Most interestingly, the two highest impact score nodes identified by BONITA included known drug targets. Thus, BONITA is a powerful approach to prioritize not only pathways but also specific mechanistic role of genes compared to existing methods. BONITA is available at: https://github.com/thakar-lab/BONITA.

2016 - Environ. Model. Softw.
The diversity of socio-economic pathways and CO2 emissions scenarios: Insights from the investigation of a scenarios database

The new scenario framework developed by the climate change research community rests on the fundamental logic that a diversity of socio-economic pathways can lead to the same radiative forcing, and therefore that a given level of radiative forcing can have very different socio-economic impacts. We propose a methodology that implements a "scenario discovery" cluster analysis and systematically identifies diverse groups of scenarios that share common outcomes among a database of socio-economic scenarios. We demonstrate the methodology with two examples using the Shared Socio-economic Pathways framework. We find that high emissions scenarios can be associated with either high or low per capita GDP growth, and that high productivity growth and catch-up are not necessarily associated with high per capita GDP and high emissions. We adapt scenario discovery cluster analysis to explore socioeconomic scenario diversity.A diversity of scenarios with high cumulative CO2 emissions is explored.High emissions scenarios can be associated with either high or low per capita GDP growth.Diverse scenarios can correspond to any of the Shared Socioeconomic Pathways domains.

2010
Chapter 14:Adverse Outcome Pathways: A Way of Linking Chemical Structure to In Vivo Toxicological Hazards

There are many national and international efforts to assess the hazards or risks of chemical substances—in particular industrial organic compounds—to humans and the environment. It is generally agreed that establishing the adequacy of information for each endpoint to be evaluated is the first step i...

2011 - The Journal of Biological Chemistry
The Ethylmalonyl-CoA Pathway Is Used in Place of the Glyoxylate Cycle by Methylobacterium extorquens AM1 during Growth on Acetate*

Background: The ethylmalonyl-CoA pathway represents an alternative to the glyoxylate cycle. Results: The ethylmalonyl-CoA pathway operates during acetate growth of Methylobacterium extorquens and represents one of three entry points into central metabolism. Conclusion: Isocitrate lyase-positive and -negative bacteria differ substantially in overall metabolic flux distribution. Significance: Tight coordination must exist for operation of the citric acid cycle in conjunction with the ethylmalonyl-CoA pathway. Acetyl-CoA assimilation was extensively studied in organisms harboring the glyoxylate cycle. In this study, we analyzed the metabolism of the facultative methylotroph Methylobacterium extorquens AM1, which lacks isocitrate lyase, the key enzyme in the glyoxylate cycle, during growth on acetate. MS/MS-based proteomic analysis revealed that the protein repertoire of M. extorquens AM1 grown on acetate is similar to that of cells grown on methanol and includes enzymes of the ethylmalonyl-CoA (EMC) pathway that were recently shown to operate during growth on methanol. Dynamic 13C labeling experiments indicate the presence of distinct entry points for acetate: the EMC pathway and the TCA cycle. 13C steady-state metabolic flux analysis showed that oxidation of acetyl-CoA occurs predominantly via the TCA cycle and that assimilation occurs via the EMC pathway. Furthermore, acetyl-CoA condenses with the EMC pathway product glyoxylate, resulting in malate formation. The latter, also formed by the TCA cycle, is converted to phosphoglycerate by a reaction sequence that is reversed with respect to the serine cycle. Thus, the results obtained in this study reveal the utilization of common pathways during the growth of M. extorquens AM1 on C1 and C2 compounds, but with a major redirection of flux within the central metabolism. Furthermore, our results indicate that the metabolic flux distribution is highly complex in this model methylotroph during growth on acetate and is fundamentally different from organisms using the glyoxylate cycle.

1999 - Molecular biology and evolution
Patterns of evolutionary rate variation among genes of the anthocyanin biosynthetic pathway.

The anthocyanin biosynthetic pathway is responsible for the production of anthocyanin pigments in plant tissues and shares a number of enzymes with other biochemical pathways. The six core structural genes of this pathway have been cloned and characterized in two taxonomically diverse plant species (maize and snapdragon). We have recently cloned these genes for a third species, the common morning glory, Ipomoea purpurea. This additional information provides an opportunity to examine patterns of evolution among genes within a single biochemical pathway. We report here that upstream genes in the anthocyanin pathway have evolved substantially more slowly than downstream genes and suggest that this difference in evolutionary rates may be explained by upstream genes being more constrained because they participate in several different biochemical pathways. In addition, regulatory genes associated with the anthocyanin pathway tend to evolve more rapidly than the structural genes they regulate, suggesting that adaptive evolution of flower color may be mediated more by regulatory than by structural genes. Finally, for individual anthocyanin genes, we found an absence of rate heterogeneity among three major angiosperm lineages. This rate constancy contrasts with an accelerated rate of evolution of three CHS-like genes in the Ipomoea lineage, indicating that these three genes have diverged without coordinated adjustment by other pathway genes.

1998 - The Journal of Bone & Joint Surgery
The Coonrad-Morrey Total Elbow Arthroplasty in Patients Who Have Rheumatoid Arthritis. A Ten to Fifteen-Year Follow-up Study*

Sixty-nine patients (seventy-eight elbows) who had rheumatoid arthritis were managed with a Coonrad-Morrey total elbow arthroplasty between 1981 and 1986. At the time of the present review, forty-one patients (forty-six elbows) were alive and had been followed for at least ten years after the procedure (Group 1). The remaining twenty-eight patients (thirty-two elbows) had died or had had a revision less than ten years after the procedure or had been followed for less than ten years (Group 2). The patients in Group 1 had a younger mean age at the time of the procedure, but all other preoperative parameters were similar for both groups. At the latest follow-up evaluation, 97 per cent of the elbows (forty-five of the forty-six in Group 1 and thirty-one of the thirty-two in Group 2) were not painful or were only mildly painful. The mean arc of flexion-extension was 28 to 131 degrees; this represents an increase of 13 degrees (15 degrees in Group 1 and 7 degrees in Group 2) compared with the preoperative value. The mean arc of pronation was 68 degrees, and the mean arc of supination was 62 degrees; this represents an increase of 21 degrees. The results for seventy-four of the seventy-eight elbows (all forty-six in Group 1 and twenty-eight of the thirty-two in Group 2) were considered satisfactory by the patients. One patient thought that the status of the elbow was unchanged compared with preoperatively, and three thought that it was worse. Seventy-six of the seventy-eight elbows had long-term radiographic evaluation; the two remaining elbows were excluded because a resection arthroplasty had been performed. There were two loose ulnar components; one was associated with an infection, and the other had been causing no symptoms at the time of the patient's death. In addition, both components were radiographically loose in an elbow that had had a revision without cement after a previous total elbow arthroplasty. Five bushings (7 per cent) were completely worn, and six (8 per cent) were partially worn. Complications occurred in eleven elbows (14 per cent) and were serious, necessitating reoperation, in ten (13 per cent). Delayed complications included three avulsions of the triceps, two deep infections, two ulnar fractures, and one fracture of an ulnar component. In addition, two elbows were revised because of aseptic loosening. No patient had persistent ulnar neuritis or serious skin complications. At the latest clinical follow-up evaluation, according to the Mayo elbow performance score, forty-three of the seventy-eight elbows had an excellent result; twenty-six, a good result; seven, a fair result; and two (both in Group 2), a poor result. The rate of survival of the prosthesis was 92.4 per cent, with 86 per cent good or excellent and 14 per cent fair or poor results.

2004 - African Affairs
Rwanda, ten years on: From genocide to dictatorship

In the spring of 1994, a small and poor country hitherto unknown to the public at large suddenly became international front-page news. Following the shooting down of President Habyarimana’s aircraft, a low-intensity civil war that had started in 1990 and been supposedly ended by the Arusha Accord (August 1993) resumed; a genocide and large-scale massacres claimed the lives of over a million Rwandans between 7 April and the beginning of July 1994. Although the violence could be seen almost live on television, the international community did nothing to stop the carnage. The United Nations peace-keeping mission United Nations Assistance Mission for Rwanda (UNAMIR) was all but withdrawn and it took weeks to formally recognize the violence for what it was — genocide.

2009 - Methods in molecular biology
Pathway and network analysis with high-density allelic association data.

Network and pathway analysis tools are traditionally used to interrogate gene expression data in order to understand the biological processes affected by a particular manipulation or disease/condition of interest. A systems-level understanding of the biological processes affected in particular disease states can allow one to identify candidates not only for pharmaceutical intervention but also for potential prognostic and diagnostic markers for the disease. However, network and pathway analyses are currently underutilized in the interpretation of large-scale genetic association study results. While simple monogenic, overtly Mendelian diseases are easily understood in the context of a single genetic aberration, the vast majority of diseases follow more complex patterns of inheritance and are influenced by a large number of genes and environmental stimuli. Genetic association studies investigating complex diseases that exploit network and pathway analysis tools can shed light on the genetic networks affected by particular genetic variations and sequence polymorphisms, just as gene expression studies can reveal genes dysregulated in a particular disease state. In this chapter, we describe the steps required to undertake network analysis of large-scale genetic association data - in particular single nucleotide polymorphism (SNP)-based genetic association data - in terms of data organization/preparation, SNP weighting schemes, and pathway analysis methods. We provide two illustrative examples that demonstrate the application of this approach: one involving the analysis of cancer tumor resequencing studies and another involving a genome-wide association study (GWAS).

1996 - Science
Nanorod-Superconductor Composites: A Pathway to Materials with High Critical Current Densities

Most large-scale applications of the high-temperature copper oxide superconductors (HTSCs) require high critical current densities (Jc's) at temperatures near the boiling point of liquid nitrogen to be technologically useful, although thermally activated flux flow reduces Jc dramatically at these temperatures. This intrinsic limitation can be overcome by introducing nanometer-sized columnar defects into an HTSC. Nanorods of magnesium oxide were grown and incorporated into HTSCs to form nanorod-HTSC composites. In this way, a high density of nanorod columnar defects can be created with orientations perpendicular and parallel to the copper oxide planes. The Jc's of the nanorod-HTSC composites are enhanced dramatically at high temperatures and magnetic fields as compared with reference samples; these composites may thus represent a technologically viable strategy for overcoming thermally activated flux flow in large-scale applications.

2014 - Neurobiology of Aging
A genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations

Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease that causes progressive motor neuron death. Although the etiology of sALS remains unknown, genetic variants are thought to predispose individuals to the disease. Several recent genome-wide association studies have identified a number of loci that increase sALS susceptibility, but these only explain a small proportion of the disease. To extend the current genetic evidence and to identify novel candidates of sALS, we performed a pooling genome-wide association study by 859,311 autosomal single-nucleotide polymorphisms of IlluminaHumanOmniZhongHua-8 combining pathway analysis in 250 typical sALS cases precluding age, clinical course, and phenotype interference and 250 control subjects from Chinese Han populations (CHP). The results revealed that 8 novel loci of 1p34.3, 3p21.1, 3p22.2, 10p15.2, 22q12.1, 3q13.11, 11q25, 12q24.33, and 5 previously reported loci of CNTN4 (kgp11325216), ATXN1 (kgp8327591), C9orf72 (kgp6016770), ITPR2 (kgp3041552), and SOD1 (kgp10760302) were associated with sALS from CHP. Furthermore, the pathway analysis based on the Gene Set Analysis Toolkit V2 showed that 10 top pathways were strongly associated with sALS from CHP, and among them, the 7 most potentially candidate pathways were phosphatidylinositol signaling system, Wnt signaling pathway, axon guidance, MAPK signaling pathway, neurotrophin signaling pathway, arachidonic acid metabolism, and T-cell receptor signaling pathway, a total of 39 significantly associate genes in 7 candidate pathways was suggested to involve in the pathogenesis of sALS from CHP. In conclusion, our results revealed several new loci and pathways related to sALS from CHP and extend the association evidence for partial loci, genes, and pathways, which were previously identified in other populations. Thus, our data provided new clues for exploring the pathogenesis of sALS.

2012 - Artificial intelligence in medicine
On mining clinical pathway patterns from medical behaviors

OBJECTIVE Clinical pathway analysis, as a pivotal issue in ensuring specialized, standardized, normalized and sophisticated therapy procedures, is receiving increasing attention in the field of medical informatics. Clinical pathway pattern mining is one of the most important components of clinical pathway analysis and aims to discover which medical behaviors are essential/critical for clinical pathways, and also where temporal orders of these medical behaviors are quantified with numerical bounds. Even though existing clinical pathway pattern mining techniques can tell us which medical behaviors are frequently performed and in which order, they seldom precisely provide quantified temporal order information of critical medical behaviors in clinical pathways. METHODS This study adopts process mining to analyze clinical pathways. The key contribution of the paper is to develop a new process mining approach to find a set of clinical pathway patterns given a specific clinical workflow log and minimum support threshold. The proposed approach not only discovers which critical medical behaviors are performed and in which order, but also provides comprehensive knowledge about quantified temporal orders of medical behaviors in clinical pathways. RESULTS The proposed approach is evaluated via real-world data-sets, which are extracted from Zhejiang Huzhou Central hospital of China with regard to six specific diseases, i.e., bronchial lung cancer, gastric cancer, cerebral hemorrhage, breast cancer, infarction, and colon cancer, in two years (2007.08-2009.09). As compared to the general sequence pattern mining algorithm, the proposed approach consumes less processing time, generates quite a smaller number of clinical pathway patterns, and has a linear scalability in terms of execution time against the increasing size of data sets. CONCLUSION The experimental results indicate the applicability of the proposed approach, based on which it is possible to discover clinical pathway patterns that can cover most frequent medical behaviors that are most regularly encountered in clinical practice. Therefore, it holds significant promise in research efforts related to the analysis of clinical pathways.

Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges

Atul J. Butte
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Purvesh Khatri
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Marina Sirota
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A. Butte
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P. Khatri
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M. Sirota

Abstract:Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis.

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