This package provides a higher-level interface to continuous-time Markov multi-state models for panel (interval-censored) data. Seven canonical clinical process structures are supplied with structurally valid generator matrices, so that transition matrices and starting values need not be constructed by hand. Panel data can be simulated from exact trajectories under regular or irregular observation schedules, with optional exactly observed absorption times and optional Weibull holding times for assessing the Markov assumption. A single fitting call validates the input against the assumed structure and returns the estimated generator with confidence intervals, mean sojourn times, transition probability matrices and observed transition counts, together with the optimiser's convergence code. A Monte Carlo driver reports Monte Carlo standard errors alongside bias, root mean squared error and interval coverage. Likelihood evaluation is delegated to msm (Jackson, 2011, <doi:10.18637/jss.v038.i08>); the panel-data likelihood is that of Kalbfleisch and Lawless (1985) <doi:10.1080/01621459.1985.10478195>.

Screens daily streamflow time series for temporal trends and change-points. This package has been primarily developed for assessing the quality of daily streamflow time series. It also contains tools for plotting and calculating many different streamflow metrics. The package can be used to produce summary screening plots showing change-points and significant temporal trends for high flow, low flow, and/or baseflow statistics, or it can be used to perform more detailed hydrological time series analyses. The package was designed for screening daily streamflow time series from Water Survey Canada and the United States Geological Survey but will also work with streamflow time series from many other agencies. Package update to version 2.0 made updates to read.flows function to allow loading of GRDC and ROBIN streamflow record formats. This package uses the `changepoint` package for change point detection. For more information on change point methods, see the changepoint package at <https://cran.r-project.org/package=changepoint>.

Addressing crucial research questions often necessitates a small sample size due to factors such as distinctive target populations, rarity of the event under study, time and cost constraints, ethical concerns, or group-level unit of analysis. Many readily available analytic methods, however, do not accommodate small sample sizes, and the choice of the best method can be unclear. The npboottprm package enables the execution of nonparametric bootstrap tests with pooled resampling to help fill this gap. Grounded in the statistical methods for small sample size studies detailed in Dwivedi, Mallawaarachchi, and Alvarado (2017) <doi:10.1002/sim.7263>, the package facilitates a range of statistical tests, encompassing independent t-tests, paired t-tests, and one-way Analysis of Variance (ANOVA) F-tests. The nonparboot() function undertakes essential computations, yielding detailed outputs which include test statistics, effect sizes, confidence intervals, and bootstrap distributions. Further, npboottprm incorporates an interactive shiny web application, nonparboot_app(), offering intuitive, user-friendly data exploration.

This package provides a comprehensive toolkit for statistical and machine learning-based analysis of long-term Natural Resource Management (NRM) datasets. Integrates formula-driven approaches, statistical inference, and machine learning (ML) models for advanced analytics. Modules cover trend and structural analysis (Mann-Kendall test, slope estimation, Chow test, structural break detection), multivariate system modelling (Partial Least Squares (PLS), Structural Equation Modelling (SEM)), response curve optimisation, time-series forecasting (Autoregressive Integrated Moving Average (ARIMA), hybrid models), panel data and treatment effects (Difference-in-Differences (DiD), causal machine learning), uncertainty and sensitivity analysis (bootstrap, Monte Carlo, Bayesian), and automated model selection and performance comparison. Designed for long-term datasets covering soil, water, crop, and climate domains. Key references: Mann and Kendall (1945) <doi:10.2307/1907187>; Sen (1968) <doi:10.1080/01621459.1968.10480934>; Bai and Perron (2003) <doi:10.1002/jae.659>; Rosseel (2012) <doi:10.18637/jss.v048.i02>; Croissant and Millo (2008) <doi:10.18637/jss.v027.i02>.

Under- and over-dispersed binary data are modeled using an extended Poisson process model (EPPM) appropriate for binary data. A feature of the model is that the under-dispersion relative to the binomial distribution only needs to be greater than zero, but the over-dispersion is restricted compared to other distributional models such as the beta and correlated binomials. Because of this, the examples focus on under-dispersed data and how, in combination with the beta or correlated distributions, flexible models can be fitted to data displaying both under- and over-dispersion. Using Generalized Linear Model (GLM) terminology, the functions utilize linear predictors for the probability of success and scale-factor with various link functions for p, and log link for scale-factor, to fit a variety of models relevant to areas such as bioassay. Details of the EPPM are in Faddy and Smith (2012) <doi:10.1002/bimj.201100214> and Smith and Faddy (2019) <doi:10.18637/jss.v090.i08>.

Look up genes, variants and proteins from R, without writing a client for every biological web service. Each service gets one client that makes the request and returns a table. Parsing is a separate function that needs no network, so it can run on a saved response and be tested offline. Transport, retries, caching and error handling are left to the biohttp package. Dependencies for single services are optional, so you do not install what you will not use. The services covered include Ensembl', described in Dyer et al. (2025) <doi:10.1093/nar/gkae1071>, UniProt', in The UniProt Consortium (2025) <doi:10.1093/nar/gkae1010>, gnomAD', in Chen et al. (2024) <doi:10.1038/s41586-023-06045-0>, Open Targets', in Buniello et al. (2025) <doi:10.1093/nar/gkae1128>, and the AlphaFold Protein Structure Database, in Varadi et al. (2024) <doi:10.1093/nar/gkad1011>. Each client's help page cites the service it calls.

Compare functional enrichment between two experimentally-derived groups of genes or proteins (Peterson, DR., et al.(2018)) <doi: 10.1371/journal.pone.0198139>. Given a list of gene symbols, diffEnrich will perform differential enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) REST API. This package provides a number of functions that are intended to be used in a pipeline. Briefly, the user provides a KEGG formatted species id for either human, mouse or rat, and the package will download and clean species specific ENTREZ gene IDs and map them to their respective KEGG pathways by accessing KEGG's REST API. KEGG's API is used to guarantee the most up-to-date pathway data from KEGG. Next, the user will identify significantly enriched pathways from two gene sets, and finally, the user will identify pathways that are differentially enriched between the two gene sets. In addition to the analysis pipeline, this package also provides a plotting function.

This package implements several methods to meta-analyze studies that report the sample median of the outcome. The methods described by McGrath et al. (2019) <doi:10.1002/sim.8013>, Ozturk and Balakrishnan (2020) <doi:10.1002/sim.8738>, and McGrath et al. (2020a) <doi:10.1002/bimj.201900036> can be applied to directly meta-analyze the median or difference of medians between groups. Additionally, a number of methods (e.g., McGrath et al. (2020b) <doi:10.1177/0962280219889080>, Cai et al. (2021) <doi:10.1177/09622802211047348>, and McGrath et al. (2023) <doi:10.1177/09622802221139233>) are implemented to estimate study-specific (difference of) means and their standard errors in order to estimate the pooled (difference of) means. Methods for meta-analyzing median survival times (McGrath et al. (2026) <doi:10.1002/sim.70533>) are also implemented. See McGrath et al. (2024) <doi:10.1002/jrsm.1686> for a detailed guide on using the package.

Conduct a noncompartmental analysis with industrial strength. Some features are 1) Use of CDISC SDTM terms 2) Automatic or manual slope selection 3) Supporting both linear-up linear-down and linear-up log-down method 4) Interval(partial) AUCs with linear or log interpolation method 5) Steady-state analysis over the dosing interval (AUCTAU, CAVG, CL and Vz from AUCTAU) 6) Installation/Operational Qualification (IQ/OQ) reports in pdf. After installation, qualify the package in your own environment: run IQNCA() for Installation Qualification and OQNCA() for Operational Qualification. Run writeMD5NCA() once after installation so the IQ file-integrity check passes. To approve a report, sign it digitally in Adobe Acrobat Reader (generate with sigField=TRUE, or run addSigFieldNCA(), to add click-to-sign fields), instead of printing and scanning; or use signPDFNCA()/verifyPDFNCA() for a scriptable signature. * Reference: Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016. (ISBN:9198299107).

Pre-testing and diagnostic tools for panel data analysis. Researchers should run these tests before any panel regression to verify modelling assumptions. The package implements: (1) the Hsiao (2014, <ISBN:978-1-107-65763-2>) homogeneity F-tests (F1/F2/F3), Swamy (1970) <doi:10.2307/1913012> parameter heterogeneity test, and Pesaran (2004) <doi:10.2139/ssrn.572504> cross-sectional dependence test via xtpretest(); (2) missing-data detection, mechanism testing, and imputation for unbalanced panels via xtmispanel(); (3) quantile-regression cross-sectional dependence tests (T_tau and T-tilde_tau statistics) of Demetrescu, Hosseinkouchack and Rodrigues (2023) via xtcsdq(); and (4) the panel quantile-regression slope homogeneity S-hat and D-hat statistics of Galvao, Juhl, Montes-Rojas and Olmo (2017) <doi:10.1093/jjfinec/nbx016> via xtqsh(). Together these tests address three fundamental pre-testing questions: (i) are slopes homogeneous? (ii) is there cross-sectional dependence? and (iii) is the panel balanced and is missingness ignorable?

This package contains all the formulae of the growth and trace element uptake model described in the equally-named Geoscientific Model Development paper (de Winter, 2017, <doi:10.5194/gmd-2017-137>). The model takes as input a file with X- and Y-coordinates of digitized growth increments recognized on a longitudinal cross section through the bivalve shell, as well as a BMP file of an elemental map of the cross section surface with chemically distinct phases separated by phase analysis. It proceeds by a step-by-step process described in the paper, by which digitized growth increments are used to calculate changes in shell height, shell thickness, shell volume, shell mass and shell growth rate through the bivalve's life time. Then, results of this growth modelling are combined with the trace element mapping results to trace the incorporation of trace elements into the bivalve shell. Results of various modelling parameters can be exported in the form of XLSX files.

preciseTAD provides functions to predict the location of boundaries of topologically associated domains (TADs) and chromatin loops at base-level resolution. As an input, it takes BED-formatted genomic coordinates of domain boundaries detected from low-resolution Hi-C data, and coordinates of high-resolution genomic annotations from ENCODE or other consortia. preciseTAD employs several feature engineering strategies and resampling techniques to address class imbalance, and trains an optimized random forest model for predicting low-resolution domain boundaries. Translated on a base-level, preciseTAD predicts the probability for each base to be a boundary. Density-based clustering and scalable partitioning techniques are used to detect precise boundary regions and summit points. Compared with low-resolution boundaries, preciseTAD boundaries are highly enriched for CTCF, RAD21, SMC3, and ZNF143 signal and more conserved across cell lines. The pre-trained model can accurately predict boundaries in another cell line using CTCF, RAD21, SMC3, and ZNF143 annotation data for this cell line.

An implementation of logistic normal multinomial (LNM) clustering. It is an extension of LNM mixture model proposed by Fang and Subedi (2020) <doi:10.1038/s41598-023-41318-8>, and is designed for clustering compositional data. The package includes 3 extended models: LNM Factor Analyzer (LNM-FA), LNM Bicluster Mixture Model (LNM-BMM) and Penalized LNM Factor Analyzer (LNM-FA). There are several advantages of LNM models: 1. LNM provides more flexible covariance structure; 2. Factor analyzer can reduce the number of parameters to estimate; 3. Bicluster can simultaneously cluster subjects and taxa, and provides significant biological insights; 4. Penalty term allows sparse estimation in the covariance matrix. Details for model assumptions and interpretation can be found in papers: Tu and Subedi (2023) <doi:10.1007/s00357-023-09452-0> and Tu and Subedi (2022) <doi:10.3329/jsr.v56i2.67469>. It also include a Biclustering algorithm that applies to multivariate normal data: Tu and Subedi (2022) <doi:10.1002/sam.11555>.

This package provides a modular framework for exact multi-objective spatial planning using mixed-integer programming. The package supports the definition of planning problems through planning units, features, management actions, action effects, spatial relations, targets, constraints, and objective functions. It enables the optimisation of spatial planning portfolios under considerations such as boundary structure, connectivity, and fragmentation. Supported multi-objective methods include weighted-sum aggregation, epsilon-constraint, and the augmented epsilon-constraint method. Problems can be solved with several commercial and open-source optimisation solvers. Optional solver backends include the gurobi R package, which is distributed with the Gurobi Optimizer installation <https://docs.gurobi.com/projects/optimizer/en/13.0/reference/r/setup.html>, and the rcbc R package, available from GitHub at <https://github.com/dirkschumacher/rcbc>. For background on multi-objective optimisation methods, see Halffmann et al. (2022) <doi:10.1002/mcda.1780>; for the augmented epsilon-constraint method, see Mavrotas (2009) <doi:10.1016/j.amc.2009.03.037>.

Power of non-parametric Mann-Kendall test and Spearmanâ s Rho test is highly influenced by serially correlated data. To address this issue, trend tests may be applied on the modified versions of the time series data by Block Bootstrapping (BBS), Prewhitening (PW) , Trend Free Prewhitening (TFPW), Bias Corrected Prewhitening and Variance Correction Approach by calculating effective sample size. Mann, H. B. (1945).<doi:10.1017/CBO9781107415324.004>. Kendall, M. (1975). Multivariate analysis. Charles Griffin&Company Ltd,. sen, P. K. (1968).<doi:10.2307/2285891>. à nöz, B., & Bayazit, M. (2012) <doi:10.1002/hyp.8438>. Hamed, K. H. (2009).<doi:10.1016/j.jhydrol.2009.01.040>. Yue, S., & Wang, C. Y. (2002) <doi:10.1029/2001WR000861>. Yue, S., Pilon, P., Phinney, B., & Cavadias, G. (2002) <doi:10.1002/hyp.1095>. Hamed, K. H., & Ramachandra Rao, A. (1998) <doi:10.1016/S0022-1694(97)00125-X>. Yue, S., & Wang, C. Y. (2004) <doi:10.1023/B:WARM.0000043140.61082.60>.

An application to calculate a patient's pretest probability (PTP) for obstructive Coronary Artery Disease (CAD) from a collection of guidelines or studies. Guidelines usually comes from the American Heart Association (AHA), American College of Cardiology (ACC) or European Society of Cardiology (ESC). Examples of PTP scores that comes from studies are the 2020 Winther et al. basic, Risk Factor-weighted Clinical Likelihood (RF-CL) and Coronary Artery Calcium Score-weighted Clinical Likelihood (CACS-CL) models <doi:10.1016/j.jacc.2020.09.585>, 2019 Reeh et al. basic and clinical models <doi:10.1093/eurheartj/ehy806> and 2017 Fordyce et al. PROMISE Minimal-Risk Tool <doi:10.1001/jamacardio.2016.5501>. As diagnosis of CAD involves a costly and invasive coronary angiography procedure for patients, having a reliable PTP for CAD helps doctors to make better decisions during patient management. This ensures high risk patients can be diagnosed and treated early for CAD while avoiding unnecessary testing for low risk patients.

This package provides tools for working with temporal discounting data, designed for behavioural researchers to simplify data cleaning/scoring and model fitting. The package implements widely used methods such as computing indifference points from adjusting amount task (Frye et al., 2016, <doi:10.3791/53584>), testing for non-systematic discounting per the criteria of Johnson & Bickel (2008, <doi:10.1037/1064-1297.16.3.264>), scoring questionnaires according to the methods of Kirby et al. (1999, <doi:10.1037//0096-3445.128.1.78>) and Wileyto et al (2004, <doi:10.3758/BF03195548>), Bayesian model selection using a range of discount functions (Franck et al., 2015, <doi:10.1002/jeab.128>), drift diffusion models of discounting (Peters & D'Esposito, 2020, <doi:10.1371/journal.pcbi.1007615>), and model-agnostic measures of discounting such as area under the curve (Myerson et al., 2001, <doi:10.1901/jeab.2001.76-235>) and ED50 (Yoon & Higgins, 2008, <doi:10.1016/j.drugalcdep.2007.12.011>).

Implementations of the k-means, hierarchical agglomerative and DBSCAN clustering methods for functional data which allows for jointly aligning and clustering curves. It supports functional data defined on one-dimensional domains but possibly evaluating in multivariate codomains. It supports functional data defined in arrays but also via the fd and funData classes for functional data defined in the fda and funData packages respectively. It currently supports shift, dilation and affine warping functions for functional data defined on the real line and uses the SRVF framework to handle boundary-preserving warping for functional data defined on a specific interval. Main reference for the k-means algorithm: Sangalli L.M., Secchi P., Vantini S., Vitelli V. (2010) "k-mean alignment for curve clustering" <doi:10.1016/j.csda.2009.12.008>. Main reference for the SRVF framework: Tucker, J. D., Wu, W., & Srivastava, A. (2013) "Generative models for functional data using phase and amplitude separation" <doi:10.1016/j.csda.2012.12.001>.

This package implements conformal prediction methods for constructing prediction intervals (regression) and prediction sets (classification) with finite-sample coverage guarantees. Methods include split conformal, CV+ and Jackknife+ (Barber et al. 2021) <doi:10.1214/20-AOS1965>, Conformalized Quantile Regression (Romano et al. 2019) <doi:10.48550/arXiv.1905.03222>, Adaptive Prediction Sets (Romano, Sesia, Candes 2020) <doi:10.48550/arXiv.2006.02544>, Regularized Adaptive Prediction Sets (Angelopoulos et al. 2021) <doi:10.48550/arXiv.2009.14193>, Mondrian conformal prediction for group-conditional coverage (Vovk, Gammerman, and Shafer 2005) <doi:10.1007/b106715>, weighted conformal prediction for covariate shift (Tibshirani et al. 2019) <doi:10.48550/arXiv.1904.06019>, and adaptive conformal inference for sequential prediction (Gibbs and Candes 2021) <doi:10.48550/arXiv.2106.00170>. All methods are distribution-free and provide calibrated uncertainty quantification without parametric assumptions. Works with any model that can produce predictions from new data, including lm', glm', ranger', xgboost', and custom user-defined models.

This package performs partial verification bias (PVB) correction for binary diagnostic tests, where PVB arises from selective patient verification in diagnostic accuracy studies. Supports correction of important accuracy measures -- sensitivity, specificity, positive predictive values and negative predictive value -- under missing-at-random and missing-not-at-random missing data mechanisms. Available methods and references are "Begg and Greenes methods" in Alonzo & Pepe (2005) <doi:10.1111/j.1467-9876.2005.00477.x> and deGroot et al. (2011) <doi:10.1016/j.annepidem.2010.10.004>; "Multiple imputation" in Harel & Zhou (2006) <doi:10.1002/sim.2494>, "EM-based logistic regression" in Kosinski & Barnhart (2003) <doi:10.1111/1541-0420.00019>; "Inverse probability weighting" in Alonzo & Pepe (2005) <doi:10.1111/j.1467-9876.2005.00477.x>; "Inverse probability bootstrap sampling" in Nahorniak et al. (2015) <doi:10.1371/journal.pone.0131765> and Arifin & Yusof (2022) <doi:10.3390/diagnostics12112839>; "Scaled inverse probability resampling methods" in Arifin & Yusof (2025) <doi:10.1371/journal.pone.0321440>.

An algorithm for flexible conditional density estimation based on application of pooled hazard regression to an artificial repeated measures dataset constructed by discretizing the support of the outcome variable. To facilitate flexible estimation of the conditional density, the highly adaptive lasso, a non-parametric regression function shown to estimate cadlag (RCLL) functions at a suitably fast convergence rate, is used. The use of pooled hazards regression for conditional density estimation as implemented here was first described for by DÃ az and van der Laan (2011) <doi:10.2202/1557-4679.1356>. Building on the conditional density estimation utilities, non-parametric inverse probability weighted (IPW) estimators of the causal effects of additive modified treatment policies are implemented, using conditional density estimation to estimate the generalized propensity score. Non-parametric IPW estimators based on this can be coupled with undersmoothing of the generalized propensity score estimator to attain the semi-parametric efficiency bound (per Hejazi, DÃ az, and van der Laan <doi:10.48550/arXiv.2205.05777>).

Compute the standard suite of climate indices from daily weather observations. Provides the canonical ETCCDI 27 (Expert Team on Climate Change Detection and Indices), the ET-SCI heatwave and cold-wave families plus the Excess Heat Factor of Nairn and Fawcett (2013), and agroclimatic, drought, and human-comfort families. Drought indices ('SPI', SPEI') accept a choice of distribution (gamma or Pearson III for SPI; log-logistic or generalised extreme value for SPEI). Reference evapotranspiration is available via Hargreaves and the FAO-56 Penman-Monteith method (Allen et al. 1998). Percentile-based indices support the Zhang (2005) in-base bootstrap. Daily inputs are numeric vectors plus a Date vector; outputs are tidy data frames. Optional gridded support via terra applies any index over a SpatRaster and reads netCDF input. No external API calls; pairs with data packages such as readnoaa'. References: Alexander et al. (2006) <doi:10.1029/2005JD006290>; Zhang et al. (2011) <doi:10.1002/wcc.147>; Zhang et al. (2005) <doi:10.1175/JCLI3366.1>.

Creating, optimizing and refining data nuggets. Data nuggets reduce a large dataset into a small collection of nuggets of data, each containing a center (location), weight (importance), and scale (variability) parameter. Data nugget centers are selected based on a space-filling maximum-entropy scheme. Data nugget weights are created by counting the number observations closest to a given data nugget center. We then say the data nugget contains these observations and the data nugget center is recalculated as the mean of these observations. Data nugget scales are created by calculating the trace of the covariance matrix of the observations contained within a data nugget divided by the dimension of the dataset. The optimal number of data nuggets is determined data-driven based on the relative second-order differences of propensity score indices. Data nuggets are refined by splitting data nuggets which have high scales or elongated shapes (defined as the ratio of the two largest eigenvalues of the covariance matrix of the observations contained within the data nugget).

This package provides a comprehensive generalized framework for parameter estimation and Generalized Process Capability Indices (GPCIs) under uncensored data using Importance Sampling (ImpSam). Supports user-supplied probability density functions (PDF/PMF), cumulative distribution functions (CDF), and survival functions (SF). Computes classical and generalized capability indices including Cpy (Maiti et al., 2010 <doi:10.1080/16843703.2010.11673233>), Spmk (Dey & Saha, 2019 <doi:10.1080/00949655.2019.1671980>), CpTk (Saha et al., 2019), Cpc (Saha et al., 2022 <doi:10.1080/02664763.2021.1971632>), CNpmc (Alotaibi et al., 2022 <doi:10.1155/2022/3135264>), CNpmkc (Saha et al., 2024 <doi:10.1142/S021853932450013X>), CNpk (Saha et al., 2018 <doi:10.1080/21681015.2018.1437793>), and Vannman's Cp(u,v) family. Generates parameter and GPCI MCMC chains via Sampling Importance Resampling (SIR) after burn-in and thinning. Provides point estimates, bias, MSE, risk values, Highest Posterior Density (HPD) intervals at 90, 95, and 99 percent levels of significance, Heidelberger and Welch MCMC convergence diagnostic, and convergence probability.