Analysis of Alternative Polyadenylation Using 3' End-Linked Reads

A computational method developed for model-based analysis of alternative polyadenylation (APA) using 3' end-linked reads. It accurately assigns 3' RNA-seq reads to polyA sites through statistical modeling, and generates multiple statistics for APA analysis. Please also see Li WV, Zheng D, Wang R, Tian B (2021) .

Prototype of Multiple Latent Dirichlet Allocation Runs

Determine a Prototype from a number of runs of Latent Dirichlet Allocation (LDA) measuring its similarities with S-CLOP: A procedure to select the LDA run with highest mean pairwise similarity, which is measured by S-CLOP (Similarity of multiple sets by Clustering with Local Pruning), to all other runs. LDA runs are specified by its assignments leading to estimators for distribution parameters. Repeated runs lead to different results, which we encounter by choosing the most representative LDA run as prototype.

Finder of Rare Entities (FiRE)

The algorithm assigns rareness/ outlierness score to every sample in voluminous datasets. The algorithm makes multiple estimations of the proximity between a pair of samples, in low-dimensional spaces. To compute proximity, FiRE uses Sketching, a variant of locality sensitive hashing. For more details: Jindal, A., Gupta, P., Jayadeva and Sengupta, D., 2018. Discovery of rare cells from voluminous single cell expression data. Nature Communications, 9(1), p.4719. .

Stratified Randomized Experiments

Estimate average treatment effects (ATEs) in stratified randomized experiments. 'sreg' is designed to accommodate scenarios with multiple treatments and cluster-level treatment assignments, and accommodates optimal linear covariate adjustment based on baseline observable characteristics. 'sreg' computes estimators and standard errors based on Bugni, Canay, Shaikh (2018) ; Bugni, Canay, Shaikh, Tabord-Meehan (2024+) ; and Jiang, Linton, Tang, Zhang (2023+) .

Assign Treatments, Power Calculations, Balances, Impact Evaluation of Experiments

Assists in the whole process of designing and evaluating Randomized Control Trials. Robust treatment assignment by strata/blocks, that handles misfits; Power calculations of the minimum detectable treatment effect or minimum populations; Balance tables of T-test of covariates; Balance Regression: (treatment ~ all x variables) with F-test of null model; Impact_evaluation: Impact evaluation regressions. This function gives you the option to include control_vars, fixed effect variables, cluster variables (for robust SE), multiple endogenous variables and multiple heterogeneous variables (to test treatment effect heterogeneity) summary_statistics: Function that creates a summary statistics table with statistics rank observations in n groups: Creates a factor variable with n groups. Each group has a min and max label attach to each category. Athey, Susan, and Guido W. Imbens (2017) .

Implement Covariate-Adaptive Randomization

Implementing seven Covariate-Adaptive Randomization to assign patients to two treatments. Three of these procedures can also accommodate quantitative and mixed covariates. Given a set of covariates, the user can generate a single sequence of allocations or replicate the design multiple times by simulating the patients' covariate profiles. At the end, an extensive assessment of the performance of the randomization procedures is provided, calculating several imbalance measures. See Baldi Antognini A, Frieri R, Zagoraiou M and Novelli M (2022) for details.

Detecting Influence Paths with Information Theory

Traces information spread through interactions between features, utilising information theory measures and a higher-order generalisation of the concept of widest paths in graphs. In particular, 'vistla' can be used to better understand the results of high-throughput biomedical experiments, by organising the effects of the investigated intervention in a tree-like hierarchy from direct to indirect ones, following the plausible information relay circuits. Due to its higher-order nature, 'vistla' can handle multi-modality and assign multiple roles to a single feature.

Parentage Assignment using Bi-Allelic Genetic Markers

Can be used for paternity and maternity assignment and outperforms conventional methods where closely related individuals occur in the pool of possible parents. The method compares the genotypes of offspring with any combination of potentials parents and scores the number of mismatches of these individuals at bi-allelic genetic markers (e.g. Single Nucleotide Polymorphisms). It elaborates on a prior exclusion method based on the Homozygous Opposite Test (HOT; Huisman 2017 ) by introducing the additional exclusion criterion HIPHOP (Homozygous Identical Parents, Heterozygous Offspring are Precluded; Cockburn et al., in revision). Potential parents are excluded if they have more mismatches than can be expected due to genotyping error and mutation, and thereby one can identify the true genetic parents and detect situations where one (or both) of the true parents is not sampled. Package 'hiphop' can deal with (a) the case where there is contextual information about parentage of the mother (i.e. a female has been seen to be involved in reproductive tasks such as nest building), but paternity is unknown (e.g. due to promiscuity), (b) where both parents need to be assigned, because there is no contextual information on which female laid eggs and which male fertilized them (e.g. polygynandrous mating system where multiple females and males deposit young in a common nest, or organisms with external fertilisation that breed in aggregations). For details: Cockburn, A., Penalba, J.V.,Jaccoud, D.,Kilian, A., Brouwer, L., Double, M.C., Margraf, N., Osmond, H.L., van de Pol, M. and Kruuk, L.E.B. (in revision). HIPHOP: improved paternity assignment among close relatives using a simple exclusion method for bi-allelic markers. Molecular Ecology Resources, DOI to be added upon acceptance.

Spatio-Network Generalised Linear Mixed Models for Areal Unit and Network Data

Implements a class of univariate and multivariate spatio-network generalised linear mixed models for areal unit and network data, with inference in a Bayesian setting using Markov chain Monte Carlo (MCMC) simulation. The response variable can be binomial, Gaussian, or Poisson. Spatial autocorrelation is modelled by a set of random effects that are assigned a conditional autoregressive (CAR) prior distribution following the Leroux model (Leroux et al. (2000) ). Network structures are modelled by a set of random effects that reflect a multiple membership structure (Browne et al. (2001) ).

Leveraging eQTLs to Identify Individual-Level Tissue of Interest for a Complex Trait

Genetic predisposition for complex traits is often manifested through multiple tissues of interest at different time points in the development. As an example, the genetic predisposition for obesity could be manifested through inherited variants that control metabolism through regulation of genes expressed in the brain and/or through the control of fat storage in the adipose tissue by dysregulation of genes expressed in adipose tissue. We present a method eGST (eQTL-based genetic subtyper) that integrates tissue-specific eQTLs with GWAS data for a complex trait to probabilistically assign a tissue of interest to the phenotype of each individual in the study. eGST estimates the posterior probability that an individual's phenotype can be assigned to a tissue based on individual-level genotype data of tissue-specific eQTLs and marginal phenotype data in a genome-wide association study (GWAS) cohort. Under a Bayesian framework of mixture model, eGST employs a maximum a posteriori (MAP) expectation-maximization (EM) algorithm to estimate the tissue-specific posterior probability across individuals. Methodology is available from: A Majumdar, C Giambartolomei, N Cai, MK Freund, T Haldar, T Schwarz, J Flint, B Pasaniuc (2019) .