Allows for building drug response models using screening data between bulk RNA-Seq and a drug response metric and two additional tools for biomarker discovery that have been developed by the Huang Laboratory at University of Minnesota. There are 3 main functions within this package. (1) calcPhenotype is used to build drug response models on RNA-Seq data and impute them on any other RNA-Seq dataset given to the model. (2) GLDS is used to calculate the general level of drug sensitivity, which can improve biomarker discovery. (3) IDWAS can take the results from calcPhenotype and link the imputed response back to available genomic (mutation and CNV alterations) to identify biomarkers. Each of these functions comes from a paper from the Huang research laboratory. Below gives the relevant paper for each function. calcPhenotype - Geeleher et al, Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines. GLDS - Geeleher et al, Cancer biomarker discovery is improved by accounting for variability in general levels of drug sensitivity in pre-clinical models. IDWAS - Geeleher et al, Discovering novel pharmacogenomic biomarkers by imputing drug response in cancer patients from large genomics studies.

Early generation breeding trials are to be conducted in multiple environments where it may not be possible to replicate all the lines in each environment due to scarcity of resources. For such situations, partially replicated (p-Rep) designs have wide application potential as only a proportion of the test lines are replicated at each environment. A collection of several utility functions related to p-Rep designs have been developed. Here, the package contains six functions for a complete stepwise analytical study of these designs. Five functions pRep1(), pRep2(), pRep3(), pRep4() and pRep5(), are used to generate five new series of p-Rep designs and also compute average variance factors and canonical efficiency factors of generated designs. A fourth function NCEV() is used to generate incidence matrix (N), information matrix (C), canonical efficiency factor (E) and average variance factor (V). This function is general in nature and can be used for studying the characterization properties of any block design. A construction procedure for p-Rep designs was given by Williams et al.(2011) <doi:10.1002/bimj.201000102> which was tedious and time consuming. Here, in this package, five different methods have been given to generate p-Rep designs easily.

Offers a convenient pipeline to test and compare various missing data imputation algorithms on simulated and real data. These include simpler methods, such as mean and median imputation and random replacement, but also include more sophisticated algorithms already implemented in popular R packages, such as mi', described by Su et al. (2011) <doi:10.18637/jss.v045.i02>; mice', described by van Buuren and Groothuis-Oudshoorn (2011) <doi:10.18637/jss.v045.i03>; missForest', described by Stekhoven and Buhlmann (2012) <doi:10.1093/bioinformatics/btr597>; missMDA', described by Josse and Husson (2016) <doi:10.18637/jss.v070.i01>; and pcaMethods', described by Stacklies et al. (2007) <doi:10.1093/bioinformatics/btm069>. The central assumption behind missCompare is that structurally different datasets (e.g. larger datasets with a large number of correlated variables vs. smaller datasets with non correlated variables) will benefit differently from different missing data imputation algorithms. missCompare takes measurements of your dataset and sets up a sandbox to try a curated list of standard and sophisticated missing data imputation algorithms and compares them assuming custom missingness patterns. missCompare will also impute your real-life dataset for you after the selection of the best performing algorithm in the simulations. The package also provides various post-imputation diagnostics and visualizations to help you assess imputation performance.

Create interactive manhattan, Q-Q and volcano plots that are usable from the R console, in Dash apps, in the RStudio viewer pane, in R Markdown documents, and in Shiny apps. Hover the mouse pointer over a point to show details or drag a rectangle to zoom. A manhattan plot is a popular graphical method for visualizing results from high-dimensional data analysis such as a (epi)genome wide association study (GWAS or EWAS), in which p-values, Z-scores, test statistics are plotted on a scatter plot against their genomic position. Manhattan plots are used for visualizing potential regions of interest in the genome that are associated with a phenotype. Interactive manhattan plots allow the inspection of specific value (e.g. rs number or gene name) by hovering the mouse over a cell, as well as zooming into a region of the genome (e.g. a chromosome) by dragging a rectangle around the relevant area. This work is based on the qqman package and the plotly.js engine. It produces similar manhattan and Q-Q plots as the manhattan and qq functions in the qqman package, with the advantage of including extra annotation information and interactive web-based visualizations directly from R. Once uploaded to a plotly account, plotly graphs (and the data behind them) can be viewed and modified in a web browser.

Estimate the abundance of cell clones from the distribution of lengths of DNA fragments (as created by sonication, whence `sonicLength'). The algorithm in "Estimating abundances of retroviral insertion sites from DNA fragment length data" by Berry CC, Gillet NA, Melamed A, Gormley N, Bangham CR, Bushman FD. Bioinformatics; 2012 Mar 15;28(6):755-62 is implemented. The experimental setting and estimation details are described in detail there. Briefly, integration of new DNA in a host genome (due to retroviral infection or gene therapy) can be tracked using DNA sequencing, potentially allowing characterization of the abundance of individual cell clones bearing distinct integration sites. The locations of integration sites can be determined by fragmenting the host DNA (via sonication or fragmentase), breaking the newly integrated DNA at a known sequence, amplifying the fragments containing both host and integrated DNA, sequencing those amplicons, then mapping the host sequences to positions on the reference genome. The relative number of fragments containing a given position in the host genome estimates the relative abundance of cells hosting the corresponding integration site, but that number is not available and the count of amplicons per fragment varies widely. However, the expected number of distinct fragment lengths is a function of the abundance of cells hosting an integration site at a given position and a certain nuisance parameter. The algorithm implicitly estimates that function to estimate the relative abundance.

Application of the Partitioning-Around-Medoids (PAM) clustering algorithm described in Schubert, E. and Rousseeuw, P.J.: "Fast and eager k-medoids clustering: O(k) runtime improvement of the PAM, CLARA, and CLARANS algorithms." Information Systems, vol. 101, p. 101804, (2021). <doi:10.1016/j.is.2021.101804>. It uses a binary format for storing and retrieval of matrices developed for the jmatrix package but the functionality of jmatrix is included here, so you do not need to install it. Also, it is used by package scellpam', so if you have installed it, you do not need to install this package. PAM can be applied to sets of data whose dissimilarity matrix can be very big. It has been tested with up to 100.000 points. It does this with the help of the code developed for other package, jmatrix', which allows the matrix not to be loaded in R memory (which would force it to be of double type) but it gets from disk, which allows using float (or even smaller data types). Moreover, the dissimilarity matrix is calculated in parallel if the computer has several cores so it can open many threads. The initial part of the PAM algorithm can be done with the BUILD or LAB algorithms; the BUILD algorithm has been implemented in parallel. The optimization phase implements the FastPAM1 algorithm, also in parallel. Finally, calculation of silhouette is available and also implemented in parallel.

Data on multiple individuals through time are often sampled at times that differ between persons. Irregular observation times can severely complicate the statistical analysis of the data. The broken stick model approximates each subjectâ s trajectory by one or more connected line segments. The times at which segments connect (breakpoints) are identical for all subjects and under control of the user. A well-fitting broken stick model effectively transforms individual measurements made at irregular times into regular trajectories with common observation times. Specification of the model requires three variables: time, measurement and subject. The model is a special case of the linear mixed model, with time as a linear B-spline and subject as the grouping factor. The main assumptions are: subjects are exchangeable, trajectories between consecutive breakpoints are straight, random effects follow a multivariate normal distribution, and unobserved data are missing at random. The package contains functions for fitting the broken stick model to data, for predicting curves in new data and for plotting broken stick estimates. The package supports two optimization methods, and includes options to structure the variance-covariance matrix of the random effects. The analyst may use the software to smooth growth curves by a series of connected straight lines, to align irregularly observed curves to a common time grid, to create synthetic curves at a user-specified set of breakpoints, to estimate the time-to-time correlation matrix and to predict future observations. See <doi:10.18637/jss.v106.i07> for additional documentation on background, methodology and applications.

Especially when cross-sectional data are observational, effects of treatment selection bias and confounding are best revealed by using Nonparametric and Unsupervised methods to "Design" the analysis of the given data ...rather than the collection of "designed data". Specifically, the "effect-size distribution" that best quantifies a potentially causal relationship between a numeric y-Outcome variable and either a binary t-Treatment or continuous e-Exposure variable needs to consist of BLOCKS of relatively well-matched experimental units (e.g. patients) that have the most similar X-confounder characteristics. Since our NU Learning approach will form BLOCKS by "clustering" experimental units in confounder X-space, the implicit statistical model for learning is One-Way ANOVA. Within Block measures of effect-size are then either [a] LOCAL Treatment Differences (LTDs) between Within-Cluster y-Outcome Means ("new" minus "control") when treatment choice is Binary or else [b] LOCAL Rank Correlations (LRCs) when the e-Exposure variable is numeric with (hopefully many) more than two levels. An Instrumental Variable (IV) method is also provided so that Local Average y-Outcomes (LAOs) within BLOCKS may also contribute information for effect-size inferences when X-Covariates are assumed to influence Treatment choice or Exposure level but otherwise have no direct effects on y-Outcomes. Finally, a "Most-Like-Me" function provides histograms of effect-size distributions to aid Doctor-Patient (or Researcher-Society) communications about Heterogeneous Outcomes. Obenchain and Young (2013) <doi:10.1080/15598608.2013.772821>; Obenchain, Young and Krstic (2019) <doi:10.1016/j.yrtph.2019.104418>.

Function gmcmtx0() computes a more reliable (general) correlation matrix. Since causal paths from data are important for all sciences, the package provides many sophisticated functions. causeSummBlk() and causeSum2Blk() give easy-to-interpret causal paths. Let Z denote control variables and compare two flipped kernel regressions: X=f(Y, Z)+e1 and Y=g(X, Z)+e2. Our criterion Cr1 says that if |e1*Y|>|e2*X| then variation in X is more "exogenous or independent" than in Y, and the causal path is X to Y. Criterion Cr2 requires |e2|<|e1|. These inequalities between many absolute values are quantified by four orders of stochastic dominance. Our third criterion Cr3, for the causal path X to Y, requires new generalized partial correlations to satisfy |r*(x|y,z)|< |r*(y|x,z)|. The function parcorVec() reports generalized partials between the first variable and all others. The package provides several R functions including get0outliers() for outlier detection, bigfp() for numerical integration by the trapezoidal rule, stochdom2() for stochastic dominance, pillar3D() for 3D charts, canonRho() for generalized canonical correlations, depMeas() measures nonlinear dependence, and causeSummary(mtx) reports summary of causal paths among matrix columns. Portfolio selection: decileVote(), momentVote(), dif4mtx(), exactSdMtx() can rank several stocks. Functions whose names begin with boot provide bootstrap statistical inference, including a new bootGcRsq() test for "Granger-causality" allowing nonlinear relations. A new tool for evaluation of out-of-sample portfolio performance is outOFsamp(). Panel data implementation is now included. See eight vignettes of the package for theory, examples, and usage tips. See Vinod (2019) \doi10.1080/03610918.2015.1122048.

This package provides a collection of functions for directional data (including massive data, with millions of observations) analysis. Hypothesis testing, discriminant and regression analysis, MLE of distributions and more are included. The standard textbook for such data is the "Directional Statistics" by Mardia, K. V. and Jupp, P. E. (2000). Other references include: a) Paine J.P., Preston S.P., Tsagris M. and Wood A.T.A. (2018). "An elliptically symmetric angular Gaussian distribution". Statistics and Computing 28(3): 689-697. <doi:10.1007/s11222-017-9756-4>. b) Tsagris M. and Alenazi A. (2019). "Comparison of discriminant analysis methods on the sphere". Communications in Statistics: Case Studies, Data Analysis and Applications 5(4):467--491. <doi:10.1080/23737484.2019.1684854>. c) Paine J.P., Preston S.P., Tsagris M. and Wood A.T.A. (2020). "Spherical regression models with general covariates and anisotropic errors". Statistics and Computing 30(1): 153--165. <doi:10.1007/s11222-019-09872-2>. d) Tsagris M. and Alenazi A. (2024). "An investigation of hypothesis testing procedures for circular and spherical mean vectors". Communications in Statistics-Simulation and Computation, 53(3): 1387--1408. <doi:10.1080/03610918.2022.2045499>. e) Yu Z. and Huang X. (2024). A new parameterization for elliptically symmetric angular Gaussian distributions of arbitrary dimension. Electronic Journal of Statistics, 18(1): 301--334. <doi:10.1214/23-EJS2210>. f) Tsagris M. and Alzeley O. (2024). "Circular and spherical projected Cauchy distributions: A Novel Framework for Circular and Directional Data Modeling". Australian & New Zealand Journal of Statistics (Accepted for publication). <doi:10.1111/anzs.12434>. g) Tsagris M., Papastamoulis P. and Kato S. (2024). "Directional data analysis: spherical Cauchy or Poisson kernel-based distribution". Statistics and Computing (Accepted for publication). <doi:10.48550/arXiv.2409.03292>.

This package provides a first step in the data analysis of Mass Spectrometry (MS) based proteomics data is to identify peptides and proteins. With this respect the huge number of experimental mass spectra typically have to be assigned to theoretical peptides derived from a sequence database. Search engines are used for this purpose. These tools compare each of the observed spectra to all candidate theoretical spectra derived from the sequence data base and calculate a score for each comparison. The observed spectrum is then assigned to the theoretical peptide with the best score, which is also referred to as the peptide to spectrum match (PSM). It is of course crucial for the downstream analysis to evaluate the quality of these matches. Therefore False Discovery Rate (FDR) control is used to return a reliable list PSMs. The FDR, however, requires a good characterisation of the score distribution of PSMs that are matched to the wrong peptide (bad target hits). In proteomics, the target decoy approach (TDA) is typically used for this purpose. The TDA method matches the spectra to a database of real (targets) and nonsense peptides (decoys). A popular approach to generate these decoys is to reverse the target database. Hence, all the PSMs that match to a decoy are known to be bad hits and the distribution of their scores are used to estimate the distribution of the bad scoring target PSMs. A crucial assumption of the TDA is that the decoy PSM hits have similar properties as bad target hits so that the decoy PSM scores are a good simulation of the target PSM scores. Users, however, typically do not evaluate these assumptions. To this end we developed TargetDecoy to generate diagnostic plots to evaluate the quality of the target decoy method.

This package provides methods for the interpolation of large spatial datasets. This package uses a basis function approach that provides a surface fitting method that can approximate standard spatial data models. Using a large number of basis functions allows for estimates that can come close to interpolating the observations (a spatial model with a small nugget variance.) Moreover, the covariance model for this method can approximate the Matern covariance family but also allows for a multi-resolution model and supports efficient computation of the profile likelihood for estimating covariance parameters. This is accomplished through compactly supported basis functions and a Markov random field model for the basis coefficients. These features lead to sparse matrices for the computations and this package makes of the R spam package for sparse linear algebra. An extension of this version over previous ones ( < 5.4 ) is the support for different geometries besides a rectangular domain. The Markov random field approach combined with a basis function representation makes the implementation of different geometries simple where only a few specific R functions need to be added with most of the computation and evaluation done by generic routines that have been tuned to be efficient. One benefit of this package's model/approach is the facility to do unconditional and conditional simulation of the field for large numbers of arbitrary points. There is also the flexibility for estimating non-stationary covariances and also the case when the observations are a linear combination (e.g. an integral) of the spatial process. Included are generic methods for prediction, standard errors for prediction, plotting of the estimated surface and conditional and unconditional simulation. See the LatticeKrigRPackage GitHub repository for a vignette of this package. Development of this package was supported in part by the National Science Foundation Grant 1417857 and the National Center for Atmospheric Research.

omicsViewer visualizes ExpressionSet (or SummarizedExperiment) in an interactive way. The omicsViewer has a separate back- and front-end. In the back-end, users need to prepare an ExpressionSet that contains all the necessary information for the downstream data interpretation. Some extra requirements on the headers of phenotype data or feature data are imposed so that the provided information can be clearly recognized by the front-end, at the same time, keep a minimum modification on the existing ExpressionSet object. The pure dependency on R/Bioconductor guarantees maximum flexibility in the statistical analysis in the back-end. Once the ExpressionSet is prepared, it can be visualized using the front-end, implemented by shiny and plotly. Both features and samples could be selected from (data) tables or graphs (scatter plot/heatmap). Different types of analyses, such as enrichment analysis (using Bioconductor package fgsea or fisher's exact test) and STRING network analysis, will be performed on the fly and the results are visualized simultaneously. When a subset of samples and a phenotype variable is selected, a significance test on means (t-test or ranked based test; when phenotype variable is quantitative) or test of independence (chi-square or fisher’s exact test; when phenotype data is categorical) will be performed to test the association between the phenotype of interest with the selected samples. Additionally, other analyses can be easily added as extra shiny modules. Therefore, omicsViewer will greatly facilitate data exploration, many different hypotheses can be explored in a short time without the need for knowledge of R. In addition, the resulting data could be easily shared using a shiny server. Otherwise, a standalone version of omicsViewer together with designated omics data could be easily created by integrating it with portable R, which can be shared with collaborators or submitted as supplementary data together with a manuscript.

Illustrates the concepts developed in Sarkar and Rashid (2019, ISSN:0025-5742) <http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwiH4deL3q3xAhWX73MBHR_wDaYQFnoECAUQAw&url=https%3A%2F%2Fwww.indianmathsociety.org.in%2Fmathstudent-part-2-2019.pdf&usg=AOvVaw3SY--3T6UAWUnH5-Nj6bSc>. This package helps a user guess four things (mean, MD, scaled MSD, and RMSD) before they get the SD. 1) The package displays the Empirical Cumulative Distribution Function (ECDF) of the given data. The user must choose the value of the mean by equating the areas of two colored (blue and green) regions. The package gives feedback to improve the choice until it is correct. Alternatively, the reader may continue with a different guess for the center (not necessarily the mean). 2) The user chooses the values of the Mean Deviation (MD) based on the ECDF of the deviations by equating the areas of two newly colored (blue and green) regions, with feedback from the package until the user guesses correctly. 3) The user chooses the Scaled Mean Squared Deviation (MSD) based on the ECDF of the scaled square deviations by equating the areas of two newly colored (blue and green) regions, with feedback from the package until the user guesses correctly. 4) The user chooses the Root Mean Squared Deviation (RMSD) by ensuring that its intersection with the ECDF of the deviations is at the same height as the intersection between the scaled MSD and the ECDF of the scaled squared deviations. Additionally, the intersection of two blue lines (the green dot) should fall on the vertical line at the maximum deviation. 5) Finally, if the mean is chosen correctly, only then the user can view the population SD (the same as the RMSD) and the sample SD (sqrt(n/(n-1))*RMSD) by clicking the respective buttons. If the mean is chosen incorrectly, the user is asked to correct it.

The aim of the R package treebalance is to provide functions for the computation of a large variety of (im)balance indices for rooted trees. The package accompanies the book Tree balance indices: a comprehensive survey by M. Fischer, L. Herbst, S. Kersting, L. Kuehn and K. Wicke (2023) <ISBN: 978-3-031-39799-8>, <doi:10.1007/978-3-031-39800-1>, which gives a precise definition for the terms balance index and imbalance index (Chapter 4) and provides an overview of the terminology in this manual (Chapter 2). For further information on (im)balance indices, see also Fischer et al. (2021) <https://treebalance.wordpress.com>. Considering both established and new (im)balance indices, treebalance provides (among others) functions for calculating the following 18 established indices and index families: the average leaf depth, the B1 and B2 index, the Colijn-Plazzotta rank, the normal, corrected, quadratic and equal weights Colless index, the family of Colless-like indices, the family of I-based indices, the Rogers J index, the Furnas rank, the rooted quartet index, the s-shape statistic, the Sackin index, the symmetry nodes index, the total cophenetic index and the variance of leaf depths. Additionally, we include 9 tree shape statistics that satisfy the definition of an (im)balance index but have not been thoroughly analyzed in terms of tree balance in the literature yet. These are: the total internal path length, the total path length, the average vertex depth, the maximum width, the modified maximum difference in widths, the maximum depth, the maximum width over maximum depth, the stairs1 and the stairs2 index. As input, most functions of treebalance require a rooted (phylogenetic) tree in phylo format (as introduced in ape 1.9 in November 2006). phylo is used to store (phylogenetic) trees with no vertices of out-degree one. For further information on the format we kindly refer the reader to E. Paradis (2012) <http://ape-package.ird.fr/misc/FormatTreeR_24Oct2012.pdf>.

The understanding of cancer mechanism requires the identification of genes playing a role in the development of the pathology and the characterization of their role (notably oncogenes and tumor suppressors). We present an updated version of the R/bioconductor package called MoonlightR, namely Moonlight2R, which returns a list of candidate driver genes for specific cancer types on the basis of omics data integration. The Moonlight framework contains a primary layer where gene expression data and information about biological processes are integrated to predict genes called oncogenic mediators, divided into putative tumor suppressors and putative oncogenes. This is done through functional enrichment analyses, gene regulatory networks and upstream regulator analyses to score the importance of well-known biological processes with respect to the studied cancer type. By evaluating the effect of the oncogenic mediators on biological processes or through random forests, the primary layer predicts two putative roles for the oncogenic mediators: i) tumor suppressor genes (TSGs) and ii) oncogenes (OCGs). As gene expression data alone is not enough to explain the deregulation of the genes, a second layer of evidence is needed. We have automated the integration of a secondary mutational layer through new functionalities in Moonlight2R. These functionalities analyze mutations in the cancer cohort and classifies these into driver and passenger mutations using the driver mutation prediction tool, CScape-somatic. Those oncogenic mediators with at least one driver mutation are retained as the driver genes. As a consequence, this methodology does not only identify genes playing a dual role (e.g. TSG in one cancer type and OCG in another) but also helps in elucidating the biological processes underlying their specific roles. In particular, Moonlight2R can be used to discover OCGs and TSGs in the same cancer type. This may for instance help in answering the question whether some genes change role between early stages (I, II) and late stages (III, IV). In the future, this analysis could be useful to determine the causes of different resistances to chemotherapeutic treatments. An additional mechanistic layer evaluates if there are mutations affecting the protein stability of the transcription factors (TFs) of the TSGs and OCGs, as that may have an effect on the expression of the genes.

An eikosogram (ancient Greek for probability picture) divides the unit square into rectangular regions whose areas, sides, and widths, represent various probabilities associated with the values of one or more categorical variates. Rectangle areas are joint probabilities, widths are always marginal (though possibly joint margins, i.e. marginal joint distributions of two or more variates), and heights of rectangles are always conditional probabilities. Eikosograms embed the rules of probability and are useful for introducing elementary probability theory, including axioms, marginal, conditional, and joint probabilities, and their relationships (including Bayes theorem as a completely trivial consequence). They are markedly superior to Venn diagrams for this purpose, especially in distinguishing probabilistic independence, mutually exclusive events, coincident events, and associations. They also are useful for identifying and understanding conditional independence structure. As data analysis tools, eikosograms display categorical data in a manner similar to Mosaic plots, especially when only two variates are involved (the only case in which they are essentially identical, though eikosograms purposely disallow spacing between rectangles). Unlike Mosaic plots, eikosograms do not alternate axes as each new categorical variate (beyond two) is introduced. Instead, only one categorical variate, designated the "response", presents on the vertical axis and all others, designated the "conditioning" variates, appear on the horizontal. In this way, conditional probability appears only as height and marginal probabilities as widths. The eikosogram is therefore much better suited to a response model analysis (e.g. logistic model) than is a Mosaic plot. Mosaic plots are better suited to log-linear style modelling as in discrete multivariate analysis. Of course, eikosograms are also suited to discrete multivariate analysis with each variate in turn appearing as the response. This makes it better suited than Mosaic plots to discrete graphical models based on conditional independence graphs (i.e. "Bayesian Networks" or "BayesNets"). The eikosogram and its superiority to Venn diagrams in teaching probability is described in W.H. Cherry and R.W. Oldford (2003) <https://math.uwaterloo.ca/~rwoldfor/papers/eikosograms/paper.pdf>, its value in exploring conditional independence structure and relation to graphical and log-linear models is described in R.W. Oldford (2003) <https://math.uwaterloo.ca/~rwoldfor/papers/eikosograms/independence/paper.pdf>, and a number of problems, puzzles, and paradoxes that are easily explained with eikosograms are given in R.W. Oldford (2003) <https://math.uwaterloo.ca/~rwoldfor/papers/eikosograms/examples/paper.pdf>.

The following several classes of frailty models using a penalized likelihood estimation on the hazard function but also a parametric estimation can be fit using this R package: 1) A shared frailty model (with gamma or log-normal frailty distribution) and Cox proportional hazard model. Clustered and recurrent survival times can be studied. 2) Additive frailty models for proportional hazard models with two correlated random effects (intercept random effect with random slope). 3) Nested frailty models for hierarchically clustered data (with 2 levels of clustering) by including two iid gamma random effects. 4) Joint frailty models in the context of the joint modelling for recurrent events with terminal event for clustered data or not. A joint frailty model for two semi-competing risks and clustered data is also proposed. 5) Joint general frailty models in the context of the joint modelling for recurrent events with terminal event data with two independent frailty terms. 6) Joint Nested frailty models in the context of the joint modelling for recurrent events with terminal event, for hierarchically clustered data (with two levels of clustering) by including two iid gamma random effects. 7) Multivariate joint frailty models for two types of recurrent events and a terminal event. 8) Joint models for longitudinal data and a terminal event. 9) Trivariate joint models for longitudinal data, recurrent events and a terminal event. 10) Joint frailty models for the validation of surrogate endpoints in multiple randomized clinical trials with failure-time and/or longitudinal endpoints with the possibility to use a mediation analysis model. 11) Conditional and Marginal two-part joint models for longitudinal semicontinuous data and a terminal event. 12) Joint frailty-copula models for the validation of surrogate endpoints in multiple randomized clinical trials with failure-time endpoints. 13) Generalized shared and joint frailty models for recurrent and terminal events. Proportional hazards (PH), additive hazard (AH), proportional odds (PO) and probit models are available in a fully parametric framework. For PH and AH models, it is possible to consider type-varying coefficients and flexible semiparametric hazard function. Prediction values are available (for a terminal event or for a new recurrent event). Left-truncated (not for Joint model), right-censored data, interval-censored data (only for Cox proportional hazard and shared frailty model) and strata are allowed. In each model, the random effects have the gamma or normal distribution. Now, you can also consider time-varying covariates effects in Cox, shared and joint frailty models (1-5). The package includes concordance measures for Cox proportional hazards models and for shared frailty models. 14) Competing Joint Frailty Model: A single type of recurrent event and two terminal events. 15) functions to compute power and sample size for four Gamma-frailty-based designs: Shared Frailty Models, Nested Frailty Models, Joint Frailty Models, and General Joint Frailty Models. Each design includes two primary functions: a power function, which computes power given a specified sample size; and a sample size function, which computes the required sample size to achieve a specified power. Moreover, the package can be used with its shiny application, in a local mode or by following the link below.

Deprecated. Use the ripemd crate isntead.

This package provides Arrow row format.

Use Pry as your rails console

This package provides a minimalist randomization library.

An efficient implementation of an lru cache

Fast Implementation of Gruber's Markdown in C