continuous_discover {MMUPHin} | R Documentation

## Unsupervised meta-analytical discovery and validation of continuous structures in microbial abundance data

### Description

`continuous_discover` takes as input a feature-by-sample matrix of microbial abundances. It first performs unsupervised continuous structure discovery (PCA) within each batch. Loadings of top PCs from each batch are then mapped against each other to identify "consensus" loadings that are reproducible across batches with a network community discovery approach with igraph. The identified consensus loadings/scores can be viewed as continuous structures in microbial profiles that are recurrent across batches and valid in a meta-analyitical sense. `continuous_discover` returns, among other output, the identified consensus scores for continuous structures in the provided microbial abundance profiles, as well as the consensus PC loadings which can be used to assign continuous scores to any sample with the same set of microbial features.

### Usage

    continuous_discover(feature_abd, batch, data, control)

### Arguments

`feature_abd` | feature-by-sample matrix of abundances (proportions or counts).
`batch` | name of the batch variable. This variable in data should be a factor variable and will be converted to so with a warning if otherwise.
`data` | data frame of metadata, columns must include batch.
`control` | a named list of additional control parameters. See details.

### Details

`control` should be provided as a named list of the following components (can be a subset).

normalization

  character. Similar to the `normalization` parameter in `Maaslin2` but only `"TSS"` and `"NONE"` are allowed. Default to `"TSS"` (total sum scaling).

transform

  character. Similar to the `transform` parameter in `Maaslin2` but only `"AST"` and `"LOG"` are allowed. Default to `"AST"` (arcsine square root transformation).

pseudo_count

  numeric. Pseudo count to add feature_abd before the transformation. Default to `NULL`, in which case pseudo count will be set automatically to 0 if `transform="AST"`, and half of minimal non-zero values in `feature_abd` if `transform="LOG"`.

var_perc_cutoff

  numeric. A value between 0 and 1 that indicates the percentage variability explained to cut off at for selecting top PCs in each batch. Across batches, the top PCs that in total explain more than var_perc_cutoff of the total variability will be selected for meta-analytical continuous structure discovery. Default to 0.8 (PCs included need to explain at least 80 total variability).

cos_cutoff

  numeric. A value between 0 and 1 that indicates cutoff for absolute cosine coefficients between PC loadings to construct the method's network with. Once the top PC loadings from each batch are selected, cosine coefficients between each loading pair are calculated which indicate their similarity. Loading pairs with absolute cosine coefficients surpassing cos_cutoff are then considered as associated with each other, and represented as an edge between the pair in a PC loading network. Network community discovery can then be performed on this network to identified densely connected "clusters" of PC loadings, which represent meta-analytically recurrent continuous structures.

cluster_function

  function. `cluster_function` is used to perform community structure discovery in the constructed PC loading network. This can be any of the network cluster functions provided in igraph. Default to `cluster_optimal`. Note that this option can be slow for larger datasets, in which case `cluster_fast_greedy` is recommended.

network_plot

  character. Name for the generated network figure file. Default to `"clustered_network.pdf"`. Can be set to `NULL` in which case no output will be generated.

plot_size_cutoff

  integer. Clusters with sizes smaller than or equal to plot_size_cutoff will be excluded in the visualized network. Defaul to 2 - visualized clusters must have at least three nodes (PC loadings).

diagnostic_plot

  character. Name for the generated diagnostic figure file. Default to `"continuous_diagnostic.pdf"`. Can be set to `NULL` in which case no output will be generated.

verbose

  logical. Indicates whether or not verbose information will be printed.

### Value

a list, with the following components:

consensus_scores

  matrix of identified consensus continuous scores. Columns are the identified consensus scores and rows correspond to samples in feature_abd.

consensus_loadings

  matrix of identified consensus loadings. Columns are the identified consensus scores and rows correspond to features in feature_abd.

mat_vali

  matrix of validation cosine coefficients of the identified consensus loadings. Columns correspond to the identified consensus scores and rows correspond to batches.

network, communities, mat_cos

  components for the constructed PC loading network and community discovery results. `network` is a igraph `graph` object for the constructed network of associated PC loadings. `communities` is a `communities` object for the identified consensus loading clusters in `network` (output from `control$cluster_function`). `mat_cos` is the matrix of cosine coefficients between all selected top PCs from all batches.

control

  list of additional control parameters used in the function call.

### Author(s)

Siyuan Ma, siyuanma@g.harvard.edu

### Examples

    data("CRC_abd", "CRC_meta")
    fit_continuous <- continuous_discover(feature_abd = CRC_abd,
                                          batch = "studyID",
                                          data = CRC_meta)

[Package MMUPHin version 1.1.0 Index]