scholarly journals Analysis of microbial compositions: a review of normalization and differential abundance analysis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Huang Lin ◽  
Shyamal Das Peddada
Keyword(s):  
Association Studies ◽  
Human Microbiome ◽  
Differential Abundance ◽  
Wide Range ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Relative Abundances ◽  
Microbiome Data ◽  
Differential Abundance Analysis

AbstractIncreasingly, researchers are discovering associations between microbiome and a wide range of human diseases such as obesity, inflammatory bowel diseases, HIV, and so on. The first step towards microbiome wide association studies is the characterization of the composition of human microbiome under different conditions. Determination of differentially abundant microbes between two or more environments, known as differential abundance (DA) analysis, is a challenging and an important problem that has received considerable interest during the past decade. It is well documented in the literature that the observed microbiome data (OTU/SV table) are relative abundances with an excess of zeros. Since relative abundances sum to a constant, these data are necessarily compositional. In this article we review some recent methods for DA analysis and describe their strengths and weaknesses.

scholarly journals Potential Application of Probiotics in the Prevention and Treatment of Inflammatory Bowel Diseases

Ulcers ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Silvina del Carmen ◽  
Alejandra de Moreno de LeBlanc ◽  
Anderson Miyoshi ◽  
Clarissa Santos Rocha ◽  
Vasco Azevedo ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Antioxidant Properties ◽  
Genetically Engineered ◽  
Treatment Protocols ◽  
Host Immune Responses ◽  
Beneficial Effects ◽  
Wide Range ◽  
Prevention And Treatment ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of inflammatory bowel diseases. These include changes in the gut microbiota, stimulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant properties. A brief overview of the uses of genetically engineered LAB that produce either antioxidant enzymes (such as catalase and superoxide dismutase) or anti-inflammatory cytokines (such as IL-10) will also be discussed. This paper will show that probiotics should be considered in treatment protocols of IBD since they provide many beneficial effects and can enhance the effectiveness of traditional used medicines.

scholarly journals STUDY OF PATTERNS OF DYSPLASIA IN INFLAMMATORY BOWEL DISEASES

2020 ◽  
pp. 1-3
Author(s):  
Keya Basu
Keyword(s):  
Histopathological Examination ◽  
Clinical Suspicion ◽  
Low Grade ◽  
Intestinal Involvement ◽  
Bowel Diseases ◽  
Indefinite For Dysplasia ◽  
Inflammatory Bowel ◽  
Low Grade Dysplasia ◽  
Surveillance Endoscopy

Background: Inflammatory bowel disease (IBD) comprises of Ulcerative colitis, Crohn’s disease and colitis of indeterminate type. Patients with long established IBD are at a greater risk for development of colorectal carcinoma (CRC). The best marker for cancer risk in IBD is dysplasia. IBD on biopsy can show low grade dysplasia (LGD) or high grade dysplasia (HGD) or histological features indefinite for dysplasia. Aims: 1) Determination of the incidence of LGD, HGD and CRC in IBD patients. 2) Evaluation of presence of any correlation between duration of IBD and extent of intestinal involvement by IBD and between duration of IBD and multifocality of dysplasia. Materials and Method: 393 patients with clinical suspicion of IBD were enrolled in this study. During surveillance endoscopy number of biopsy samples taken from each case were 10-15. Histopathological examination of these biopsy samples was done. Results: Out of 266 patients of IBD who turned up for surveillance endoscopy, the incidences of LGD, HGD, CRC and IBD indeterminate for dysplasia were found to be 10.90%, 4.51%, 4.51% and 2.63% respectively. On statistical analysis it was discovered that in both UC and CD the extent of intestinal involvement was directly proportional to the duration of the disease. In both UC and CD, longer disease durations were linked to more foci of dysplasia. Conclusion: In both UC and CD, longer disease durations is linked to the extent of intestinal involvement and number of foci of dysplasia while type of dysplasia (LGD/HGD) is not related to duration of IBD. In IBD with UC incidence of PSC is linked with the extent of intestinal involvement.

scholarly journals An Enzymatic Toolkit for Selective Proteolysis, Detection, and Visualization of Mucin-Domain Glycoproteins

2020 ◽  
Author(s):  
D. Judy Shon ◽  
Stacy Malaker ◽  
Kayvon Pedram ◽  
Emily Yang ◽  
Venkatesh Krishnan ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tissue Slices ◽  
Robust Detection ◽  
Wide Range ◽  
Mucin Expression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Distinct Peptide ◽  
Selective Proteolysis

<p>Densely O-glycosylated mucin domains are found in a broad range of cell surface and secreted proteins, where they play key physiological roles. In addition, alterations in mucin expression and glycosylation are common in a variety of human diseases, such as cancer, cystic fibrosis, and inflammatory bowel diseases. These correlations have been challenging to uncover and establish because tools that specifically probe mucin domains are lacking. Here, we present a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. By mutating catalytic residues of two such enzymes, we engineered mucin-selective binding agents with retained glycoform preferences. StcE<sup>E447D</sup> is a pan-mucin stain derived from enterohemorrhagic <i>Escherichia coli </i>that is tolerant to a wide range of glycoforms. BT4244<sup>E575A</sup> derived from <i>Bacteroides thetaiotaomicron</i> is selective for truncated, asialylated Core 1 structures commonly associated with malignant and pre-malignant tissues. We demonstrated that these catalytically inactive point mutants enable robust detection and visualization of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry. Application of our enzymatic toolkit to ovarian cancer patient ascites fluid and tissue slices facilitated characterization of patients based on differences in mucin cleavage and expression patterns.</p>

Rank normalization empowers a t-test for microbiome differential abundance analysis while controlling for false discoveries

2021 ◽  
Author(s):  
Matthew L Davis ◽  
Yuan Huang ◽  
Kai Wang
Keyword(s):  
T Test ◽  
Strongly Correlated ◽  
Differential Abundance ◽  
Potential Availability ◽  
Future Potential ◽  
Microbiome Data ◽  
False Discoveries ◽  
Differential Abundance Analysis ◽  
Strong Control ◽  
Normalization Factors

Abstract A major task in the analysis of microbiome data is to identify microbes associated with differing biological conditions. Before conducting analysis, raw data must first be adjusted so that counts from different samples are comparable. A typical approach is to estimate normalization factors by which all counts in a sample are multiplied or divided. However, the inherent variation associated with estimation of normalization factors are often not accounted for in subsequent analysis, leading to a loss of precision. Rank normalization is a nonparametric alternative to the estimation of normalization factors in which each count for a microbial feature is replaced by its intrasample rank. Although rank normalization has been successfully applied to microarray analysis in the past, it has yet to be explored for microbiome data, which is characterized by high frequencies of 0s, strongly correlated features and compositionality. We propose to use rank normalization as an alternative to the estimation of normalization factors and examine its performance when paired with a two-sample t-test. On a rigorous 3rd-party benchmarking simulation, it is shown to offer strong control over the false discovery rate, and at sample sizes greater than 50 per treatment group, to offer an improvement in performance over commonly used normalization factors paired with t-tests, Wilcoxon rank-sum tests and methodologies implemented by R packages. On two real datasets, it yielded valid and reproducible results that were strongly in agreement with the original findings and the existing literature, further demonstrating its robustness and future potential. Availability: The data underlying this article are available online along with R code and supplementary materials at https://github.com/matthewlouisdavisBioStat/Rank-Normalization-Empowers-a-T-Test.

scholarly journals A novel normalization and differential abundance test framework for microbiome data

2020 ◽  
Vol 36 (13) ◽  
pp. 3959-3965
Author(s):  
Yuanjing Ma ◽  
Yuan Luo ◽  
Hongmei Jiang
Keyword(s):  
Effect Size ◽  
Marker Gene ◽  
Single Species ◽  
Supplementary Information ◽  
Size Factor ◽  
Library Size ◽  
Differential Abundance ◽  
Over Dispersion ◽  
Microbiome Data ◽  
Differential Abundance Analysis

Abstract Motivation Microbial communities have been proved to have close relationship with many diseases. The identification of differentially abundant microbial species is clinically meaningful for finding disease-related pathogenic or probiotic bacteria. However, certain characteristics of microbiome data have hurdled the accuracy and effectiveness of differential abundance analysis. The abundances or counts of microbiome species are usually on different scales and exhibit zero-inflation and over-dispersion. Normalization is a crucial step before the differential abundance test. However, existing normalization methods typically try to adjust counts on different scales to a common scale by constructing size factors with the assumption that count distributions across samples are equivalent up to a certain percentile. These methods often yield undesirable results when differentially abundant species are of low to medium abundance level. For differential abundance analysis, existing methods often use a single distribution to model the dispersion of species which lacks flexibility to catch a single species’ distinctiveness. These methods tend to detect a lot of false positives and often lack of power when the effect size is small. Results We develop a novel framework for differential abundance analysis on sparse high-dimensional marker gene microbiome data. Our methodology relies on a novel network-based normalization technique and a two-stage zero-inflated mixture count regression model (RioNorm2). Our normalization method aims to find a group of relatively invariant microbiome species across samples and conditions in order to construct the size factor. Another contribution of the paper is that our testing approach can take under-sampling and over-dispersion into consideration by separating microbiome species into two groups and model them separately. Through comprehensive simulation studies, the performance of our method is consistently powerful and robust across different settings with different sample size, library size and effect size. We also demonstrate the effectiveness of our novel framework using a published dataset of metastatic melanoma and find biological insights from the results. Availability and implementation The R package ‘RioNorm2’ can be installed from Github athttps://github.com/yuanjing-ma/RioNorm2. Supplementary information Supplementary data are available at Bioinformatics online.

Fecal calprotectin in inflammatory bowel diseases: update and perspectives

2017 ◽  
Vol 55 (4) ◽  
Author(s):  
Hana Manceau ◽  
Valérie Chicha-Cattoir ◽  
Hervé Puy ◽  
Katell Peoc’h
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Therapeutic Response ◽  
Fecal Calprotectin ◽  
Intestinal Wall ◽  
Therapeutic Monitoring ◽  
Non Invasive ◽  
Bowel Diseases ◽  
Calprotectin Level ◽  
Inflammatory Bowel

AbstractInflammatory bowel diseases (IBDs) are chronic diseases that result from the inflammation of the intestinal wall, suspected in any patient presenting with intestinal symptoms. Until recently, the diagnosis was mainly based on both clinical and endoscopic arguments. The use of an easy, fast, reliable, non-invasive, and inexpensive biological assay is mandatory not only in diagnosis but also in evolutionary and therapeutic monitoring. To date, the fecal calprotectin is the most documented in this perspective. This marker allows the discrimination between functional and organic bowel processes with good performance. The determination of the fecal calprotectin level contributes to the evaluation of the degree of disease activity and to monitoring of therapeutic response.

scholarly journals Precision medicine and inflammatory bowel diseases: concept, strategies, future

2021 ◽  
Vol 1 (6) ◽  
pp. 121-129
Author(s):  
G. R. Bikbavova ◽  
M. A. Livzan ◽  
D. G. Novikov ◽  
E. A. Bambulskaya
Keyword(s):  
Precision Medicine ◽  
Inflammatory Bowel Diseases ◽  
Scientific Information ◽  
Treatment Strategies ◽  
Wide Range ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Treatment ◽  
Personalized Approach ◽  
The Right

With the advent of modern cellular and genomic technologies, we have become participants in the integration of such areas as personalized, predictive, preventive, and precision medicine (referred to as 4P-medicine), into practical healthcare. In replace of the classic methods of diagnosis and treatment of diseases comes medicine, which makes it possible to predict (anticipate) the disease, and a personalized approach to each patient, taking into account their genetic, biochemical and physiological uniqueness. Precision medicine aims to improve the quality of medical care by opening up an individual approach to the patient and covers a wide range of areas, including drug therapy, genetics, and cause-and-effect relationships in order to make the right decisions based on evidence. 4P-medicine combines knowledge in the field of proteomics, metabolomics, genomics, bioinformatics with classical approaches of anatomy, therapy, laboratory and instrumental diagnostics as well as public health. The purpose of this review is to analyze and summarize the information available to date and to present examples of the application of modern approaches of medicine into clinical practice by diving into the example of inflammatory bowel diseases (IBD). The search for literature containing scientific information about relevant studies was conducted in the PubMed and Google Scholar systems with the use of the following keywords: precision medicine, 4P medicine, inflammatory bowel diseases. Despite significant progress in medicine in general, there is still a long way to go before implementing the principles of precision medicine in the field of IBD, since many clinicians continue to treat patients with IBD symptomatically. However, the use of specific biomarkers and new treatment strategies as described in the review, can significantly accelerate this path and contribute to the improvement of diagnostic and therapeutic approaches.

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