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    Lecture 1 Data Quality and Statistics

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    dgrapov
    west coast metabolomics center, data analysis, metabolomics, summer sessions in metabolomics 2013, dmitry grapov

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    Lecture 1 Data Quality and Statistics

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    dgrapov
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    west coast metabolomics center, data analysis, metabolomics, summer sessions in metabolomics 2013, dmitry grapov

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    west coast metabolomics center, data analysis, metabolomics, summer sessions in metabolomics 2013, dmitry grapov

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    29K views31 pages

    Lecture 1 Data Quality and Statistics

    Uploaded by

    dgrapov
    west coast metabolomics center, data analysis, metabolomics, summer sessions in metabolomics 2013, dmitry grapov

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
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    At a glance
    Powered by AI
    Some of the key takeaways from the document are that metabolomic data analysis involves pre-analysis steps like normalization, outlier detection and missing value imputation to clean the data. Common statistical analyses include univariate analyses to identify statistically significant changes, bivariate analyses like correlation and regression to study relationships between two variables, and multivariate techniques like PCA and PLS-DA for classification and prediction.

    Some of the main goals of metabolomic data analysis are to identify trends in the data that may be related to analytical sources or metadata, determine differences or similarities between experimental groups, and determine what variables are predictive or related to the variables of interest.

    Common pre-analysis steps performed on metabolomic data include data quality metric assessment, normalization to account for differences in sample amounts, outlier detection to identify erroneous measurements, missing value imputation to replace missing values, and data transformation to achieve normality if needed.

    Strategies for Metabolomic Data Analysis

    Introduction

    Dmitry Grapov, PhD

    Goals?

    Metabolomics

    Analysis at the Metabolomic Scale

    Can you spot the difference?


    Univariate
    Multivariate Predictive Modeling

    Group 2

    Group 1

    ANOVA

    PCA

    PLS

    Analytical Dimensions
    variables

    Samples

    Analyzing Metabolomic Data

    Pre-analysis Data properties

    Statistical approaches
    Multivariate approaches Systems approaches

    Pre-analysis
    Data quality metrics precision accuracy Remedies normalization outliers detection missing values imputation

    Normalization
    sample-wise sum, adjusted measurement-wise transformation (normality) encoding (trigonometric, etc.)

    standard deviation
    mean

    Outliers
    single measurements (univariate)

    two compounds (bivariate)

    Outliers
    univariate/bivariate \ vs. multivariate

    outliers? mixed up samples

    Transformation
    logarithm (shifted) power (BOX-COX) inverse
    Quantile-quantile (Q-Q) plots are useful for visual overview of variable normality
    X X -0.5

    Missing Values Imputation


    Why is it missing? random systematic

    mean

    analytical
    biological

    Imputation methods
    single value (mean, min, etc.) multiple multivariate

    PCA

    Data Analysis Goals


    Exploration
    analytical sources meta data/covariates

    Classification

    Prediction

    Are there any trends in my data? Useful Methods


    matrix decomposition (PCA, ICA, NMF) cluster analysis

    Differences/similarities between groups?


    discrimination, classification, significant changes

    Useful Methods
    analysis of variance (ANOVA) partial least squares discriminant analysis (PLS-DA) Others: random forest, CART, SVM, ANN

    What is related or predictive of my variable(s) of interest?


    regression

    Useful Methods
    correlation partial least squares (PLS)

    Data Structure
    univariate: a single variable (1-D)

    bivariate: two variables (2-D)


    multivariate: 2 > variables (m-D)

    Data Types
    continuous

    discreet
    binary

    Data Complexity
    Meta Data m n samples variables Experimental Design = complexity

    Data
    m-D 1-D 2-D Variable # = dimensionality

    Univariate Analyses
    univariate properties
    length center (mean, median, geometric mean)

    dispersion (variance, standard deviation)


    Range (min / max)

    standard deviation
    mean

    Univariate Analyses
    sensitive to distribution shape

    parametric = assumes normality


    error in Y, not in X (Y = mX + error)

    optimal for long data


    assumed independence false discovery rate long

    wide n-of-one

    False Discovery Rate (FDR)


    univariate approaches do not scale well

    Type I Error: False Positives


    Type II Error: False Negatives

    Type I risk =
    1-(1-p.value)m
    m = number of variables tested

    FDR correction
    Example:
    Design: 30 sample, 300 variables Test: t-test FDR method: Benjamini and Hochberg (fdr) correction at q=0.05

    Results

    FDR adjusted p-values (fdr) or estimate of FDR (Fdr, q-value)

    Bioinformatics (2008) 24 (12):1461-1462

    Achieving significance is a function of:


    significance level () and power (1- )

    effect size (standardized difference in means)

    sample size (n)

    Bivariate Data
    relationship between two variables

    correlation (strength)
    regression (predictive) regression

    correlation

    Correlation
    Parametric (Pearson) or rank-order (Spearman, Kendall)

    correlation is covariance scaled between -1 and 1

    Correlation vs. Regression

    Regression describes the least squares or best-fitline for the relationship (Y = m*X + b)

    Geyser Example
    Goal: Dont miss eruption! Data time between eruptions
    70 14 min

    duration of eruption
    3.5 1 min

    Azzalini, A. and Bowman, A. W. (1990). A look at some data on the Old Faithful geyser. Applied Statistics 39, 357365

    Geyser Example (cont.)


    Two cluster pattern for both duration and frequency

    Azzalini, A. and Bowman, A. W. (1990). A look at some data on the Old Faithful geyser. Applied Statistics 39, 357365

    Geyser Example (cont.)


    Noted deviations from two cluster pattern
    Outliers? Covariates?

    Covariates
    Trends in data which mask primary goals can be accounted for using covariate adjustment and appropriate modeling strategies

    Geyser Example (cont.)


    Noted deviations from two cluster pattern can be explained by covariate:
    Hydrofraking

    Covariate adjustment is an integral aspect of statistical analyses (e.g. ANCOVA)

    Summary
    Data exploration and pre-analysis: increase robustness of results guards against spurious findings Can greatly improve primary analyses Univariate Statistics: are useful for identification of statically significant changes or relationships sub-optimal for wide data best when combined with advanced multivariate techniques

    Resources
    Web-based data analysis platforms MetaboAnalyst( MeltDB( )
    https://meltdb.cebitec.uni-bielefeld.de/cgi-bin/login.cgi
    http://www.metaboanalyst.ca/MetaboAnalyst/faces/Home.jsp

    Programming tools The R Project for Statistical Computing( ) Bioconductor( ) GUI tools imDEV( )
    http://www.r-project.org/ http://www.bioconductor.org/ http://sourceforge.net/projects/imdev/?source=directory

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