搜索结果：Developments in biological standardization

The Index of ADL was developed to study results of treatment and prognosis in the elderly and chronically ill. Grades of the Index summarize over-all performance in bathing, dressing, going to toilet, transferring, continence, and feeding. More than 2,000 evaluations of 1,001 individuals demonstrated use of the Index as a survey instrument, as an objective guide to the course of chronic illness, as a tool for studying the aging process, and as an aid in rehabilitation teaching. Of theoretical interest is the observation that the order of recovery of Index functions in disabled patients is remarkably similar to the order of development of primary functions in children. This parallelism, and similarity to the behavior of primitive peoples, suggests that the Index is based on primary biological and psychosocial function, reflecting the adequacy of organized neurological and locomotor response.

In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

One of the main elements of dendrochronological standardization is removing the biological trend, i.e. the progressive decline of ring width along a cross-sectional radius that is caused by the corresponding increase in stem size and tree age over time. The “conservative” option for removing this biological trend is to fit a modified negative exponential curve (or a straight line with slope ≤ 0) to the ring-width measurements. This method is based on the assumption that, especially for open-grown and/or shade-intolerant species, annual growth rate of mature trees fluctuates around a specific level, expressed by a constant ring width. Because this method has numerical and conceptual drawbacks, we propose an alternative approach based on the assumption that constant growth is expressed by a constant basal area increment distributed over a growing surface. From this starting point, we derive a mathematical expression for the biological trend of ring width, which can be easily calculated and used for dendrochronological standardization.The proposed C-method is compared to other standardization techniques, including Regional Curve Standardization (RCS), of tree-ring width from ponderosa pines (Pinus ponderosa Douglas ex P.Lawson & C.Lawson) located at the Gus Pearson Natural Area (GPNA) in northern Arizona, USA. Master ring-index chronologies built from ring area, RCS, and C-method reproduced stand-wide patterns of tree growth at the GPNA, whereas other standardization options, including the “conservative” one, failed to do so. In addition, the C-method has the advantage of calculating an expected growth curve for each tree, whereas RCS is based on applying the same growth curve to all trees. In conclusion, the C-method replaces the purely empirical “conservative” option with a theory-based approach, which is applicable to individual ring-width measurement series, does not require fitting a growth curve using nonlinear regression, and can be rigorously tested for improving tree-ring records of environmental changes.

Excess accumulation and aggregation of toxic soluble and insoluble amyloid-β species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-β deposits using monoclonal antibodies that target amyloid-β and have identified MRI signal abnormalities called amyloid-related imaging abnormalities (ARIA) as possible spontaneous or treatment-related adverse events. This review provides a comprehensive state-of-the-art conceptual review of radiological features, clinical detection and classification challenges, pathophysiology, underlying biological mechanism(s) and risk factors/predictors associated with ARIA. We summarize the existing literature and current lines of evidence with ARIA-oedema/effusion (ARIA-E) and ARIA-haemosiderosis/microhaemorrhages (ARIA-H) seen across anti-amyloid clinical trials and therapeutic development. Both forms of ARIA may occur, often early, during anti-amyloid-β monoclonal antibody treatment. Across randomized controlled trials, most ARIA cases were asymptomatic. Symptomatic ARIA-E cases often occurred at higher doses and resolved within 3-4 months or upon treatment cessation. Apolipoprotein E haplotype and treatment dosage are major risk factors for ARIA-E and ARIA-H. Presence of any microhaemorrhage on baseline MRI increases the risk of ARIA. ARIA shares many clinical, biological and pathophysiological features with Alzheimer's disease and cerebral amyloid angiopathy. There is a great need to conceptually link the evident synergistic interplay associated with such underlying conditions to allow clinicians and researchers to further understand, deliberate and investigate on the combined effects of these multiple pathophysiological processes. Moreover, this review article aims to better assist clinicians in detection (either observed via symptoms or visually on MRI), management based on appropriate use recommendations, and general preparedness and awareness when ARIA are observed as well as researchers in the fundamental understanding of the various antibodies in development and their associated risks of ARIA. To facilitate ARIA detection in clinical trials and clinical practice, we recommend the implementation of standardized MRI protocols and rigorous reporting standards. With the availability of approved amyloid-β therapies in the clinic, standardized and rigorous clinical and radiological monitoring and management protocols are required to effectively detect, monitor, and manage ARIA in real-world clinical settings.

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their "biological aging" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

Water of sufficient quality and quantity is critical to all life. Increasing human population and growth of technology require human society to devote more and more attention to protection of adequate supplies of water. Although perception of biological degradation stimulated current state and federal legislation on the quality of water resources, that biological focus was lost in the search for easily measured physical and chemical surrogates. The "fishable and swimmable" goal of the Water Pollution Control Act of 1972 (PL 92-500) and its charge to "restore and maintain" biotic integrity illustrate that law's biological underpinning. Further, the need for operational definitions of terms like "biological integrity" and "unreasonable degradation" and for ecologically sound tools to measure divergence from societal goals have increased interest in biological monitoring. Assessment of water resource quality by sampling biological communities in the field (ambient biological monitoring) is a promising approach that requires expanded use of ecological expertise. One such approach, the Index of Biotic Integrity (IBI), provides a broadly based, multiparameter tool for the assessment of biotic integrity in running waters. IBI based on fish community attributes has now been applied widely in North America. The success of IBI has stimulated the development of similar approaches using other aquatic taxa. Expanded use of ecological expertise in ambient biological monitoring is essential to the protection of water resources. Ecologists have the expertise to contribute significantly to those programs.

Abstract Aim Invasive alien species (IAS) pose a significant threat to biodiversity. The Convention on Biological Diversity’s 2010 Biodiversity Target, and the associated indicator for IAS, has stimulated globally coordinated efforts to quantify patterns in the extent of biological invasion, its impact on biodiversity and policy responses. Here, we report on the outcome of indicators of alien invasion at a global scale. Location Global. Methods We developed four indicators in a pressure‐state‐response framework, i.e. number of documented IAS (pressure), trends in the impact of IAS on biodiversity (state) and trends in international agreements and national policy adoption relevant to reducing IAS threats to biodiversity (response). These measures were considered best suited to providing globally representative, standardized and sustainable indicators by 2010. Results We show that the number of documented IAS is a significant underestimate, because its value is negatively affected by country development status and positively by research effort and information availability. The Red List Index demonstrates that IAS pressure is driving declines in species diversity, with the overall impact apparently increasing. The policy response trend has nonetheless been positive for the last several decades, although only half of countries that are signatory to the Convention on Biological Diversity (CBD) have IAS‐relevant national legislation. Although IAS pressure has apparently driven the policy response, this has clearly not been sufficient and/or adequately implemented to reduce biodiversity impact. Main conclusions For this indicator of threat to biodiversity, the 2010 Biodiversity Target has thus not been achieved. The results nonetheless provide clear direction for bridging the current divide between information available on IAS and that needed for policy and management for the prevention and control of IAS. It further highlights the need for measures to ensure that policy is effectively implemented, such that it translates into reduced IAS pressure and impact on biodiversity beyond 2010.

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.

Dietary polyphenols represent a wide variety of compounds that occur in fruits,vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They aremostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins andphenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis,anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascularprotection, improvement of the endothelial function, as well as inhibition of angiogenesisand cell proliferation activity. Most of these biological actions have been attributed to theirintrinsic reducing capabilities. They may also offer indirect protection by activatingendogenous defense systems and by modulating cellular signaling processes such asnuclear factor-kappa B (NF-кB) activation, activator protein-1(AP-1) DNA binding,glutathione biosynthesis, phosphoinositide 3 (PI3)-kinase/protein kinase B (Akt) pathway,mitogen-activated protein kinase (MAPK) proteins [extracellular signal-regulated proteinkinase (ERK), c-jun N-terminal kinase (JNK) and P38 ] activation, and the translocationinto the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2). This paper covers themost recent literature on the subject, and describes the biological mechanisms of action andprotective effects of dietary polyphenols.

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

BACKGROUND: Gene-expression analysis is increasingly important in biological research, with real-time reverse transcription PCR (RT-PCR) becoming the method of choice for high-throughput and accurate expression profiling of selected genes. Given the increased sensitivity, reproducibility and large dynamic range of this methodology, the requirements for a proper internal control gene for normalization have become increasingly stringent. Although housekeeping gene expression has been reported to vary considerably, no systematic survey has properly determined the errors related to the common practice of using only one control gene, nor presented an adequate way of working around this problem. RESULTS: We outline a robust and innovative strategy to identify the most stably expressed control genes in a given set of tissues, and to determine the minimum number of genes required to calculate a reliable normalization factor. We have evaluated ten housekeeping genes from different abundance and functional classes in various human tissues, and demonstrated that the conventional use of a single gene for normalization leads to relatively large errors in a significant proportion of samples tested. The geometric mean of multiple carefully selected housekeeping genes was validated as an accurate normalization factor by analyzing publicly available microarray data. CONCLUSIONS: The normalization strategy presented here is a prerequisite for accurate RT-PCR expression profiling, which, among other things, opens up the possibility of studying the biological relevance of small expression differences.

NPs mimic all three cellular antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Taking advantage of the physiochemical properties of nanomaterials, nanozymes have shown a broad range of applications from in vitro detection to replacing specific enzymes in living systems. With the emergence of the new concept of "nanozymology", nanozymes have now become an emerging new field connecting nanotechnology and biology. Since the landmark paper on nanozymes was published in 2007, we have extensively explored their catalytic mechanism, established the corresponding standards to quantitatively determine their catalytic activities, and opened up a broad range of applications from biological detection and environmental monitoring to disease diagnosis and biomedicine development. Here we mainly focus on our progress in the systematic design and construction of functionally specific nanozymes, the standardization of nanozyme research, and the exploration of their applications for replacing natural enzymes in living systems. We also show that, by combining the unique physicochemical properties and enzyme-like catalytic activities, nanozymes can offer a variety of multifunctional platforms with a broad of applications from in vitro detection to in vivo monitoring and therapy. For instance, targeting antibody-conjugated ferromagnetic nanozymes simultaneously provide three functions: target capture, magnetic separation, and nanozyme color development for target detection. We finally will address the prospect of nanozyme research to become "nanozymology". We expect that nanozymes with unique physicochemical properties and intrinsic enzyme-mimicking catalytic properties will attract broad interest in both fundamental research and practical applications and offer new opportunities for traditional enzymology.

Asthma and chronic obstructive pulmonary disease (COPD, also called chronic airflow limitation (CAL)) are the most frequent diagnoses in patients with intrathoracic airways obstruction [1]. Often these patients show a spontaneous variability in the degree of airways obstruction, which can be documented by serial lung function measurements. Large variability in the degree of airways obstruction is indicative of an increased susceptibility of the patient to environmental stimuli that cause acute airway narrowing. Knowledge of the potential severity of these episodes of acute airways obstruction is of clinical interest. Therefore, several quantitative measures of the response of the airways to bronchoconstrictors in vivo have been advocated over the past two decades. The objective of the present guidelines is to address the methodological issues of the various available techniques, and to provide up-to-date international guidelines on standardization. The present recommendations might not represent the potentially best methodologies. However, they do represent the currently validated techniques, by which interchangeable results can be obtained among laboratories. Variable airways obstruction can be mimicked in the laboratory by challenge tests with bronchoconstrictive stimuli (fig. 1) [2]. This enables one to measure the degree of the so-called «airway responsiveness» of the subject to a particular agent. Since the bronchoconstrictive response varies from one stimulus to another, one needs to specify the challenging agent. Therefore, the term «nonspecific» airway responsiveness should be abandoned. Figure 1– Dose-response curves to inhaled methacholine using the dosimeter method in 3 subjects. Airway hyperresponsiveness in asthma is characterised by a leftward shift of the curve (hypersensitivity), a steeper slope (hyperreactivity), and an increase in maximal response (excessive airway narrowing). Modified from de Pee et al. [243] with permission. Airway hyperresponsiveness refers to an exaggerated response to the bronchoconstrictor. This is reflected by an increased sensitivity to the stimulus, which …

A flexible statistical framework is developed for the analysis of read counts from RNA-Seq gene expression studies. It provides the ability to analyse complex experiments involving multiple treatment conditions and blocking variables while still taking full account of biological variation. Biological variation between RNA samples is estimated separately from the technical variation associated with sequencing technologies. Novel empirical Bayes methods allow each gene to have its own specific variability, even when there are relatively few biological replicates from which to estimate such variability. The pipeline is implemented in the edgeR package of the Bioconductor project. A case study analysis of carcinoma data demonstrates the ability of generalized linear model methods (GLMs) to detect differential expression in a paired design, and even to detect tumour-specific expression changes. The case study demonstrates the need to allow for gene-specific variability, rather than assuming a common dispersion across genes or a fixed relationship between abundance and variability. Genewise dispersions de-prioritize genes with inconsistent results and allow the main analysis to focus on changes that are consistent between biological replicates. Parallel computational approaches are developed to make non-linear model fitting faster and more reliable, making the application of GLMs to genomic data more convenient and practical. Simulations demonstrate the ability of adjusted profile likelihood estimators to return accurate estimators of biological variability in complex situations. When variation is gene-specific, empirical Bayes estimators provide an advantageous compromise between the extremes of assuming common dispersion or separate genewise dispersion. The methods developed here can also be applied to count data arising from DNA-Seq applications, including ChIP-Seq for epigenetic marks and DNA methylation analyses.

The main challenge for all electrical, mechanical and optical sensors is to detect low molecular weight (less than 400 Da) chemical and biological analytes under extremely dilute conditions. Surface plasmon resonance sensors are the most commonly used optical sensors due to their unique ability for real-time monitoring the molecular binding events. However, their sensitivities are insufficient to detect trace amounts of small molecular weight molecules such as cancer biomarkers, hormones, antibiotics, insecticides, and explosive materials which are respectively important for early-stage disease diagnosis, food quality control, environmental monitoring, and homeland security protection. With the rapid development of nanotechnology in the past few years, nanomaterials-enhanced surface plasmon resonance sensors have been developed and used as effective tools to sense hard-to-detect molecules within the concentration range between pmol and amol. In this review article, we reviewed and discussed the latest trend and challenges in engineering and applications of nanomaterials-enhanced surface plasmon resonance sensors (e.g., metallic nanoparticles, magnetic nanoparticles, carbon-based nanomaterials, latex nanoparticles and liposome nanoparticles) for detecting "hard-to-identify" biological and chemical analytes. Such information will be viable in terms of providing a useful platform for designing future ultrasensitive plasmonic nanosensors.

Trastuzumab-based therapy has been shown to confer overall survival benefit in HER2-positive patients with advanced gastric cancer in a large multicentric trial (ToGA study). Subgroup analysis identified adenocarcinomas of the stomach and gastroesophageal (GE) junction with overexpression of HER2 according to immunohistochemistry (IHC) as potential responders. Due to recent approval of trastuzumab for HER2 positive metastatic gastric and GE-junction cancer in Europe (EMEA) HER2 diagnostics is now mandatory with IHC being the primary test followed by fluorescence in situ hybridization (FISH) in IHC2+ cases. However, in order to not miss patients potentially responding to targeted therapy determination of a HER2-positive status for gastric cancer required modification of scoring as had been proposed in a pre-ToGA study. To validate this new HER2 status testing procedure in terms of inter-laboratory and inter-observer consensus for IHC scoring a series of 547 gastric cancer tissue samples on a tissue microarray (TMA) was used. In the first step, 30 representative cores were used to identify specific IHC HER2 scoring issues among eight French and German laboratories, while in the second step the full set of 547 cores was used to determine IHC HER2 intensity and area score concordance between six German pathologists. Specific issues relating to discordance were identified and recommendations formulated which proved to be effective to reliably determine HER2 status in a prospective test series of 447 diagnostic gastric cancer specimens.

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.

BACKGROUND: Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. RESULTS: The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. CONCLUSION: The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.