Macarron is a workflow to systematically annotate and prioritize potentially bioactive (and often unannotated) small molecules in microbial community metabolomic datasets. Macarron prioritizes metabolic features as potentially bioactive in a phenotype/condition of interest using a combination of (a) covariance with annotated metabolites, (b) ecological properties such as abundance with respect to covarying annotated compounds, and (c) differential abundance in the phenotype/condition of interest.
If you have questions, please direct it to: Macarron Forum
Macarron requires R version 4.2.0 or higher. Install Bioconductor and then install Macarron:
if(!requireNamespace("BiocManager", quietly = TRUE))
install.packages("BiocManager")
BiocManager::install("Macarron")
Macarron can be run from the command line or as an R function. Both methods require the same
arguments, have the same options, and use the same default settings. The package includes the
wrapper Macarron()
as well as functions which perform different steps in the Macarron
framework.
Macarron requires 4 comma-separated, appropriately formatted input files. The files and their formatting constraints are described below.
If you do not have the chemical taxonomy file, you can generate this file using the annotation dataframe and Macarron utility decorate_ID
(see Advanced Topics).
By default, all files will be stored in a folder named Macarron_output inside the current working directory. The main prioritization results are stored in prioritized_metabolites_all.csv
. Another file, prioritized_metabolites_characterizable.csv
is a subset of prioritized_metabolites_all.csv
and only contains metabolic features which covary with at least one annotated metabolite.
The columns in these output files are:
Maaslin2
.Example (demo) input files can be found under inst/extdata
folder of the Macarron
source. These files were generated from the PRISM study of stool metabolomes of individuals with inflammatory bowel disease (IBD) and healthy “Control” individuals. Control and IBD are the two phenotypes in this example. Macarron will be applied to prioritize metabolic features with respect to their bioactivity in IBD. Therefore, in this example, the phenotype of interest is “IBD” and the reference phenotype is “Control”. The four input files are demo_abundances.csv
, demo_annotations.csv
, demo_metadata.csv
, and demo_taxonomy.csv
.
library(Macarron)
## Loading required package: SummarizedExperiment
## Loading required package: MatrixGenerics
## Loading required package: matrixStats
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## Attaching package: 'MatrixGenerics'
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## colSums2, colTabulates, colVarDiffs, colVars, colWeightedMads,
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## Welcome to Bioconductor
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## Vignettes contain introductory material; view with
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prism_abundances <- system.file(
'extdata','demo_abundances.csv', package="Macarron")
prism_annotations <-system.file(
'extdata','demo_annotations.csv', package="Macarron")
prism_metadata <-system.file(
'extdata','demo_metadata.csv', package="Macarron")
mets_taxonomy <-system.file(
'extdata','demo_taxonomy.csv', package="Macarron")
prism_prioritized <- Macarron::Macarron(input_abundances = prism_abundances,
input_annotations = prism_annotations,
input_metadata = prism_metadata,
input_taxonomy = mets_taxonomy)
## 2023-11-28 20:41:30.980078 INFO::Creating output folder.
## 2023-11-28 20:41:30.995113 INFO::Writing function arguments to log file
## Samples with both abundances and metadata: 102
## 2023-11-28 20:41:31.055029 INFO::Summarized Experiment created.
## 2023-11-28 20:41:31.056815 INFO::Metadata chosen for prevalence filtering: diagnosis
## 869 features pass chosen minimum prevalence threshold of 0.7.
## Calculating pairwise correlations in phenotype: IBD
##
## Calculating pairwise correlations in phenotype: Control
## Distance matrix with 869 features created.
## 2023-11-28 20:41:38.037289 INFO::Distance matrix with 869 metabolic features created.
## Initiating module detection
## 2023-11-28 20:41:38.039024 INFO::Minimum module size used for this dataset: 10
## Tree constructed
## Evaluating measures of success
## ..cutHeight not given, setting it to 0.99 ===> 99% of the (truncated) height range in dendro.
## ..done.
## ..cutHeight not given, setting it to 0.99 ===> 99% of the (truncated) height range in dendro.
## ..done.
## ..cutHeight not given, setting it to 0.99 ===> 99% of the (truncated) height range in dendro.
## ..done.
## ..cutHeight not given, setting it to 0.99 ===> 99% of the (truncated) height range in dendro.
## ..done.
## ..cutHeight not given, setting it to 0.99 ===> 99% of the (truncated) height range in dendro.
## ..done.
## 2023-11-28 20:41:39.642496 INFO::Total number of modules detected: 30
## Initiating AVA calculations
## Finding anchors
## Calculating AVA
## Initiating q-value calculations
## [1] "Creating output folder"
## [1] "Creating output feature tables folder"
## [1] "Creating output fits folder"
## [1] "Creating output figures folder"
## 2023-11-28 20:41:41.59776 INFO::Writing function arguments to log file
## 2023-11-28 20:41:41.604673 INFO::Verifying options selected are valid
## 2023-11-28 20:41:41.666529 INFO::Determining format of input files
## 2023-11-28 20:41:41.668093 INFO::Input format is data samples as columns and metadata samples as rows
## 2023-11-28 20:41:41.687592 INFO::Formula for fixed effects: expr ~ diagnosis + age + antibiotics
## 2023-11-28 20:41:41.689748 INFO::Filter data based on min abundance and min prevalence
## 2023-11-28 20:41:41.690548 INFO::Total samples in data: 102
## 2023-11-28 20:41:41.69122 INFO::Min samples required with min abundance for a feature not to be filtered: 0.000000
## 2023-11-28 20:41:41.70416 INFO::Total filtered features: 0
## 2023-11-28 20:41:41.705451 INFO::Filtered feature names from abundance and prevalence filtering:
## 2023-11-28 20:41:41.728007 INFO::Total filtered features with variance filtering: 0
## 2023-11-28 20:41:41.729311 INFO::Filtered feature names from variance filtering:
## 2023-11-28 20:41:41.729998 INFO::Running selected normalization method: NONE
## 2023-11-28 20:41:41.730782 INFO::Applying z-score to standardize continuous metadata
## 2023-11-28 20:41:41.774493 INFO::Running selected transform method: NONE
## 2023-11-28 20:41:41.775934 INFO::Running selected analysis method: LM
## 2023-11-28 20:41:41.784218 INFO::Fitting model to feature number 1, F1
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## 2023-11-28 20:41:42.564621 INFO::Fitting model to feature number 185, F191
## 2023-11-28 20:41:42.568705 INFO::Fitting model to feature number 186, F192
## 2023-11-28 20:41:42.572942 INFO::Fitting model to feature number 187, F193
## 2023-11-28 20:41:42.577095 INFO::Fitting model to feature number 188, F194
## 2023-11-28 20:41:42.581131 INFO::Fitting model to feature number 189, F195
## 2023-11-28 20:41:42.585142 INFO::Fitting model to feature number 190, F196
## 2023-11-28 20:41:42.589337 INFO::Fitting model to feature number 191, F197
## 2023-11-28 20:41:42.593983 INFO::Fitting model to feature number 192, F198
## 2023-11-28 20:41:42.5983 INFO::Fitting model to feature number 193, F199
## 2023-11-28 20:41:42.602685 INFO::Fitting model to feature number 194, F200
## 2023-11-28 20:41:42.607239 INFO::Fitting model to feature number 195, F201
## 2023-11-28 20:41:42.611452 INFO::Fitting model to feature number 196, F202
## 2023-11-28 20:41:42.61563 INFO::Fitting model to feature number 197, F203
## 2023-11-28 20:41:42.619751 INFO::Fitting model to feature number 198, F204
## 2023-11-28 20:41:42.624053 INFO::Fitting model to feature number 199, F206
## 2023-11-28 20:41:42.627921 INFO::Fitting model to feature number 200, F207
## 2023-11-28 20:41:42.631566 INFO::Fitting model to feature number 201, F208
## 2023-11-28 20:41:42.636445 INFO::Fitting model to feature number 202, F209
## 2023-11-28 20:41:42.640488 INFO::Fitting model to feature number 203, F210
## 2023-11-28 20:41:42.644658 INFO::Fitting model to feature number 204, F211
## 2023-11-28 20:41:42.649158 INFO::Fitting model to feature number 205, F212
## 2023-11-28 20:41:42.653608 INFO::Fitting model to feature number 206, F213
## 2023-11-28 20:41:42.658263 INFO::Fitting model to feature number 207, F214
## 2023-11-28 20:41:42.662678 INFO::Fitting model to feature number 208, F215
## 2023-11-28 20:41:42.667093 INFO::Fitting model to feature number 209, F216
## 2023-11-28 20:41:42.67183 INFO::Fitting model to feature number 210, F217
## 2023-11-28 20:41:42.676064 INFO::Fitting model to feature number 211, F218
## 2023-11-28 20:41:42.68034 INFO::Fitting model to feature number 212, F219
## 2023-11-28 20:41:42.68497 INFO::Fitting model to feature number 213, F220
## 2023-11-28 20:41:42.689307 INFO::Fitting model to feature number 214, F221
## 2023-11-28 20:41:42.693644 INFO::Fitting model to feature number 215, F222
## 2023-11-28 20:41:42.697999 INFO::Fitting model to feature number 216, F223
## 2023-11-28 20:41:42.702508 INFO::Fitting model to feature number 217, F224
## 2023-11-28 20:41:42.706394 INFO::Fitting model to feature number 218, F225
## 2023-11-28 20:41:42.710639 INFO::Fitting model to feature number 219, F226
## 2023-11-28 20:41:42.714632 INFO::Fitting model to feature number 220, F227
## 2023-11-28 20:41:42.718497 INFO::Fitting model to feature number 221, F228
## 2023-11-28 20:41:42.722247 INFO::Fitting model to feature number 222, F229
## 2023-11-28 20:41:42.725865 INFO::Fitting model to feature number 223, F230
## 2023-11-28 20:41:42.72994 INFO::Fitting model to feature number 224, F231
## 2023-11-28 20:41:42.733768 INFO::Fitting model to feature number 225, F232
## 2023-11-28 20:41:42.737455 INFO::Fitting model to feature number 226, F233
## 2023-11-28 20:41:42.740996 INFO::Fitting model to feature number 227, F234
## 2023-11-28 20:41:42.744514 INFO::Fitting model to feature number 228, F235
## 2023-11-28 20:41:42.748295 INFO::Fitting model to feature number 229, F236
## 2023-11-28 20:41:42.752228 INFO::Fitting model to feature number 230, F237
## 2023-11-28 20:41:42.756054 INFO::Fitting model to feature number 231, F238
## 2023-11-28 20:41:42.759715 INFO::Fitting model to feature number 232, F239
## 2023-11-28 20:41:42.763473 INFO::Fitting model to feature number 233, F240
## 2023-11-28 20:41:42.767028 INFO::Fitting model to feature number 234, F241
## 2023-11-28 20:41:42.770583 INFO::Fitting model to feature number 235, F242
## 2023-11-28 20:41:42.774154 INFO::Fitting model to feature number 236, F243
## 2023-11-28 20:41:42.777786 INFO::Fitting model to feature number 237, F244
## 2023-11-28 20:41:42.781373 INFO::Fitting model to feature number 238, F245
## 2023-11-28 20:41:42.784895 INFO::Fitting model to feature number 239, F246
## 2023-11-28 20:41:42.788481 INFO::Fitting model to feature number 240, F247
## 2023-11-28 20:41:42.792097 INFO::Fitting model to feature number 241, F248
## 2023-11-28 20:41:42.795635 INFO::Fitting model to feature number 242, F249
## 2023-11-28 20:41:42.799161 INFO::Fitting model to feature number 243, F250
## 2023-11-28 20:41:42.802684 INFO::Fitting model to feature number 244, F252
## 2023-11-28 20:41:42.806184 INFO::Fitting model to feature number 245, F253
## 2023-11-28 20:41:42.809748 INFO::Fitting model to feature number 246, F254
## 2023-11-28 20:41:42.814177 INFO::Fitting model to feature number 247, F255
## 2023-11-28 20:41:42.818462 INFO::Fitting model to feature number 248, F256
## 2023-11-28 20:41:42.822549 INFO::Fitting model to feature number 249, F257
## 2023-11-28 20:41:42.826584 INFO::Fitting model to feature number 250, F259
## 2023-11-28 20:41:42.830711 INFO::Fitting model to feature number 251, F260
## 2023-11-28 20:41:42.834897 INFO::Fitting model to feature number 252, F261
## 2023-11-28 20:41:42.839026 INFO::Fitting model to feature number 253, F262
## 2023-11-28 20:41:42.843028 INFO::Fitting model to feature number 254, F263
## 2023-11-28 20:41:42.847046 INFO::Fitting model to feature number 255, F264
## 2023-11-28 20:41:42.851208 INFO::Fitting model to feature number 256, F265
## 2023-11-28 20:41:42.855296 INFO::Fitting model to feature number 257, F266
## 2023-11-28 20:41:42.859183 INFO::Fitting model to feature number 258, F267
## 2023-11-28 20:41:42.863169 INFO::Fitting model to feature number 259, F269
## 2023-11-28 20:41:42.867474 INFO::Fitting model to feature number 260, F270
## 2023-11-28 20:41:42.871565 INFO::Fitting model to feature number 261, F271
## 2023-11-28 20:41:42.875491 INFO::Fitting model to feature number 262, F272
## 2023-11-28 20:41:42.879407 INFO::Fitting model to feature number 263, F273
## 2023-11-28 20:41:42.883497 INFO::Fitting model to feature number 264, F274
## 2023-11-28 20:41:42.88754 INFO::Fitting model to feature number 265, F276
## 2023-11-28 20:41:42.891484 INFO::Fitting model to feature number 266, F277
## 2023-11-28 20:41:42.895287 INFO::Fitting model to feature number 267, F278
## 2023-11-28 20:41:42.89922 INFO::Fitting model to feature number 268, F279
## 2023-11-28 20:41:42.903199 INFO::Fitting model to feature number 269, F280
## 2023-11-28 20:41:42.907128 INFO::Fitting model to feature number 270, F281
## 2023-11-28 20:41:42.910947 INFO::Fitting model to feature number 271, F282
## 2023-11-28 20:41:42.914861 INFO::Fitting model to feature number 272, F283
## 2023-11-28 20:41:42.918799 INFO::Fitting model to feature number 273, F284
## 2023-11-28 20:41:42.922653 INFO::Fitting model to feature number 274, F285
## 2023-11-28 20:41:42.926457 INFO::Fitting model to feature number 275, F286
## 2023-11-28 20:41:42.930293 INFO::Fitting model to feature number 276, F287
## 2023-11-28 20:41:42.934292 INFO::Fitting model to feature number 277, F288
## 2023-11-28 20:41:42.938236 INFO::Fitting model to feature number 278, F289
## 2023-11-28 20:41:42.942227 INFO::Fitting model to feature number 279, F290
## 2023-11-28 20:41:42.946227 INFO::Fitting model to feature number 280, F292
## 2023-11-28 20:41:42.950234 INFO::Fitting model to feature number 281, F293
## 2023-11-28 20:41:42.954205 INFO::Fitting model to feature number 282, F294
## 2023-11-28 20:41:42.95815 INFO::Fitting model to feature number 283, F295
## 2023-11-28 20:41:42.962041 INFO::Fitting model to feature number 284, F296
## 2023-11-28 20:41:42.965773 INFO::Fitting model to feature number 285, F297
## 2023-11-28 20:41:42.969551 INFO::Fitting model to feature number 286, F298
## 2023-11-28 20:41:42.973443 INFO::Fitting model to feature number 287, F299
## 2023-11-28 20:41:42.97722 INFO::Fitting model to feature number 288, F300
## 2023-11-28 20:41:42.981249 INFO::Fitting model to feature number 289, F301
## 2023-11-28 20:41:42.985267 INFO::Fitting model to feature number 290, F302
## 2023-11-28 20:41:42.98922 INFO::Fitting model to feature number 291, F303
## 2023-11-28 20:41:42.993098 INFO::Fitting model to feature number 292, F304
## 2023-11-28 20:41:42.997259 INFO::Fitting model to feature number 293, F305
## 2023-11-28 20:41:43.00133 INFO::Fitting model to feature number 294, F306
## 2023-11-28 20:41:43.00528 INFO::Fitting model to feature number 295, F307
## 2023-11-28 20:41:43.009238 INFO::Fitting model to feature number 296, F308
## 2023-11-28 20:41:43.013338 INFO::Fitting model to feature number 297, F309
## 2023-11-28 20:41:43.01734 INFO::Fitting model to feature number 298, F310
## 2023-11-28 20:41:43.021304 INFO::Fitting model to feature number 299, F311
## 2023-11-28 20:41:43.025265 INFO::Fitting model to feature number 300, F312
## 2023-11-28 20:41:43.029307 INFO::Fitting model to feature number 301, F313
## 2023-11-28 20:41:43.033866 INFO::Fitting model to feature number 302, F315
## 2023-11-28 20:41:43.038029 INFO::Fitting model to feature number 303, F316
## 2023-11-28 20:41:43.042343 INFO::Fitting model to feature number 304, F317
## 2023-11-28 20:41:43.046596 INFO::Fitting model to feature number 305, F318
## 2023-11-28 20:41:43.050588 INFO::Fitting model to feature number 306, F319
## 2023-11-28 20:41:43.05461 INFO::Fitting model to feature number 307, F320
## 2023-11-28 20:41:43.058727 INFO::Fitting model to feature number 308, F321
## 2023-11-28 20:41:43.062754 INFO::Fitting model to feature number 309, F322
## 2023-11-28 20:41:43.06674 INFO::Fitting model to feature number 310, F323
## 2023-11-28 20:41:43.070677 INFO::Fitting model to feature number 311, F324
## 2023-11-28 20:41:43.112076 INFO::Fitting model to feature number 312, F325
## 2023-11-28 20:41:43.116627 INFO::Fitting model to feature number 313, F326
## 2023-11-28 20:41:43.12063 INFO::Fitting model to feature number 314, F327
## 2023-11-28 20:41:43.124471 INFO::Fitting model to feature number 315, F328
## 2023-11-28 20:41:43.128326 INFO::Fitting model to feature number 316, F329
## 2023-11-28 20:41:43.132351 INFO::Fitting model to feature number 317, F330
## 2023-11-28 20:41:43.136264 INFO::Fitting model to feature number 318, F331
## 2023-11-28 20:41:43.14006 INFO::Fitting model to feature number 319, F332
## 2023-11-28 20:41:43.14389 INFO::Fitting model to feature number 320, F333
## 2023-11-28 20:41:43.147735 INFO::Fitting model to feature number 321, F334
## 2023-11-28 20:41:43.151616 INFO::Fitting model to feature number 322, F335
## 2023-11-28 20:41:43.155461 INFO::Fitting model to feature number 323, F336
## 2023-11-28 20:41:43.159234 INFO::Fitting model to feature number 324, F337
## 2023-11-28 20:41:43.163249 INFO::Fitting model to feature number 325, F338
## 2023-11-28 20:41:43.167152 INFO::Fitting model to feature number 326, F339
## 2023-11-28 20:41:43.171092 INFO::Fitting model to feature number 327, F340
## 2023-11-28 20:41:43.17492 INFO::Fitting model to feature number 328, F342
## 2023-11-28 20:41:43.178664 INFO::Fitting model to feature number 329, F343
## 2023-11-28 20:41:43.182385 INFO::Fitting model to feature number 330, F344
## 2023-11-28 20:41:43.186166 INFO::Fitting model to feature number 331, F345
## 2023-11-28 20:41:43.189669 INFO::Fitting model to feature number 332, F346
## 2023-11-28 20:41:43.193169 INFO::Fitting model to feature number 333, F347
## 2023-11-28 20:41:43.196654 INFO::Fitting model to feature number 334, F348
## 2023-11-28 20:41:43.200285 INFO::Fitting model to feature number 335, F350
## 2023-11-28 20:41:43.204006 INFO::Fitting model to feature number 336, F351
## 2023-11-28 20:41:43.207761 INFO::Fitting model to feature number 337, F352
## 2023-11-28 20:41:43.21165 INFO::Fitting model to feature number 338, F353
## 2023-11-28 20:41:43.215447 INFO::Fitting model to feature number 339, F355
## 2023-11-28 20:41:43.219281 INFO::Fitting model to feature number 340, F356
## 2023-11-28 20:41:43.22336 INFO::Fitting model to feature number 341, F357
## 2023-11-28 20:41:43.227265 INFO::Fitting model to feature number 342, F358
## 2023-11-28 20:41:43.232049 INFO::Fitting model to feature number 343, F359
## 2023-11-28 20:41:43.236267 INFO::Fitting model to feature number 344, F360
## 2023-11-28 20:41:43.240328 INFO::Fitting model to feature number 345, F361
## 2023-11-28 20:41:43.244489 INFO::Fitting model to feature number 346, F362
## 2023-11-28 20:41:43.248714 INFO::Fitting model to feature number 347, F363
## 2023-11-28 20:41:43.252968 INFO::Fitting model to feature number 348, F364
## 2023-11-28 20:41:43.25717 INFO::Fitting model to feature number 349, F365
## 2023-11-28 20:41:43.261647 INFO::Fitting model to feature number 350, F366
## 2023-11-28 20:41:43.265926 INFO::Fitting model to feature number 351, F367
## 2023-11-28 20:41:43.270095 INFO::Fitting model to feature number 352, F368
## 2023-11-28 20:41:43.274323 INFO::Fitting model to feature number 353, F369
## 2023-11-28 20:41:43.279103 INFO::Fitting model to feature number 354, F370
## 2023-11-28 20:41:43.283475 INFO::Fitting model to feature number 355, F371
## 2023-11-28 20:41:43.287946 INFO::Fitting model to feature number 356, F372
## 2023-11-28 20:41:43.292551 INFO::Fitting model to feature number 357, F373
## 2023-11-28 20:41:43.296507 INFO::Fitting model to feature number 358, F374
## 2023-11-28 20:41:43.300281 INFO::Fitting model to feature number 359, F375
## 2023-11-28 20:41:43.303949 INFO::Fitting model to feature number 360, F376
## 2023-11-28 20:41:43.307568 INFO::Fitting model to feature number 361, F377
## 2023-11-28 20:41:43.311156 INFO::Fitting model to feature number 362, F378
## 2023-11-28 20:41:43.31521 INFO::Fitting model to feature number 363, F379
## 2023-11-28 20:41:43.319151 INFO::Fitting model to feature number 364, F380
## 2023-11-28 20:41:43.322953 INFO::Fitting model to feature number 365, F381
## 2023-11-28 20:41:43.326725 INFO::Fitting model to feature number 366, F382
## 2023-11-28 20:41:43.330656 INFO::Fitting model to feature number 367, F383
## 2023-11-28 20:41:43.334497 INFO::Fitting model to feature number 368, F384
## 2023-11-28 20:41:43.338368 INFO::Fitting model to feature number 369, F386
## 2023-11-28 20:41:43.342095 INFO::Fitting model to feature number 370, F387
## 2023-11-28 20:41:43.345863 INFO::Fitting model to feature number 371, F388
## 2023-11-28 20:41:43.349848 INFO::Fitting model to feature number 372, F389
## 2023-11-28 20:41:43.353733 INFO::Fitting model to feature number 373, F390
## 2023-11-28 20:41:43.357655 INFO::Fitting model to feature number 374, F391
## 2023-11-28 20:41:43.361468 INFO::Fitting model to feature number 375, F392
## 2023-11-28 20:41:43.365303 INFO::Fitting model to feature number 376, F393
## 2023-11-28 20:41:43.369265 INFO::Fitting model to feature number 377, F394
## 2023-11-28 20:41:43.373172 INFO::Fitting model to feature number 378, F395
## 2023-11-28 20:41:43.377148 INFO::Fitting model to feature number 379, F396
## 2023-11-28 20:41:43.381049 INFO::Fitting model to feature number 380, F397
## 2023-11-28 20:41:43.38486 INFO::Fitting model to feature number 381, F398
## 2023-11-28 20:41:43.388792 INFO::Fitting model to feature number 382, F399
## 2023-11-28 20:41:43.39271 INFO::Fitting model to feature number 383, F400
## 2023-11-28 20:41:43.396516 INFO::Fitting model to feature number 384, F401
## 2023-11-28 20:41:43.400347 INFO::Fitting model to feature number 385, F402
## 2023-11-28 20:41:43.40424 INFO::Fitting model to feature number 386, F403
## 2023-11-28 20:41:43.408024 INFO::Fitting model to feature number 387, F404
## 2023-11-28 20:41:43.411607 INFO::Fitting model to feature number 388, F406
## 2023-11-28 20:41:43.415026 INFO::Fitting model to feature number 389, F407
## 2023-11-28 20:41:43.418364 INFO::Fitting model to feature number 390, F408
## 2023-11-28 20:41:43.421689 INFO::Fitting model to feature number 391, F409
## 2023-11-28 20:41:43.425102 INFO::Fitting model to feature number 392, F410
## 2023-11-28 20:41:43.428762 INFO::Fitting model to feature number 393, F411
## 2023-11-28 20:41:43.432604 INFO::Fitting model to feature number 394, F412
## 2023-11-28 20:41:43.436567 INFO::Fitting model to feature number 395, F413
## 2023-11-28 20:41:43.440401 INFO::Fitting model to feature number 396, F414
## 2023-11-28 20:41:43.444535 INFO::Fitting model to feature number 397, F415
## 2023-11-28 20:41:43.448477 INFO::Fitting model to feature number 398, F416
## 2023-11-28 20:41:43.452378 INFO::Fitting model to feature number 399, F417
## 2023-11-28 20:41:43.456317 INFO::Fitting model to feature number 400, F418
## 2023-11-28 20:41:43.460241 INFO::Fitting model to feature number 401, F419
## 2023-11-28 20:41:43.464229 INFO::Fitting model to feature number 402, F420
## 2023-11-28 20:41:43.468121 INFO::Fitting model to feature number 403, F421
## 2023-11-28 20:41:43.472062 INFO::Fitting model to feature number 404, F422
## 2023-11-28 20:41:43.475925 INFO::Fitting model to feature number 405, F423
## 2023-11-28 20:41:43.47981 INFO::Fitting model to feature number 406, F425
## 2023-11-28 20:41:43.483854 INFO::Fitting model to feature number 407, F426
## 2023-11-28 20:41:43.487801 INFO::Fitting model to feature number 408, F428
## 2023-11-28 20:41:43.491705 INFO::Fitting model to feature number 409, F429
## 2023-11-28 20:41:43.495588 INFO::Fitting model to feature number 410, F430
## 2023-11-28 20:41:43.499523 INFO::Fitting model to feature number 411, F431
## 2023-11-28 20:41:43.503782 INFO::Fitting model to feature number 412, F432
## 2023-11-28 20:41:43.507685 INFO::Fitting model to feature number 413, F433
## 2023-11-28 20:41:43.51158 INFO::Fitting model to feature number 414, F434
## 2023-11-28 20:41:43.51547 INFO::Fitting model to feature number 415, F435
## 2023-11-28 20:41:43.519445 INFO::Fitting model to feature number 416, F436
## 2023-11-28 20:41:43.523446 INFO::Fitting model to feature number 417, F437
## 2023-11-28 20:41:43.527409 INFO::Fitting model to feature number 418, F438
## 2023-11-28 20:41:43.532604 INFO::Fitting model to feature number 419, F439
## 2023-11-28 20:41:43.536826 INFO::Fitting model to feature number 420, F440
## 2023-11-28 20:41:43.54093 INFO::Fitting model to feature number 421, F441
## 2023-11-28 20:41:43.545038 INFO::Fitting model to feature number 422, F442
## 2023-11-28 20:41:43.549055 INFO::Fitting model to feature number 423, F443
## 2023-11-28 20:41:43.552871 INFO::Fitting model to feature number 424, F444
## 2023-11-28 20:41:43.556834 INFO::Fitting model to feature number 425, F445
## 2023-11-28 20:41:43.560863 INFO::Fitting model to feature number 426, F446
## 2023-11-28 20:41:43.564851 INFO::Fitting model to feature number 427, F447
## 2023-11-28 20:41:43.568755 INFO::Fitting model to feature number 428, F448
## 2023-11-28 20:41:43.572564 INFO::Fitting model to feature number 429, F449
## 2023-11-28 20:41:43.576345 INFO::Fitting model to feature number 430, F450
## 2023-11-28 20:41:43.580277 INFO::Fitting model to feature number 431, F451
## 2023-11-28 20:41:43.584188 INFO::Fitting model to feature number 432, F452
## 2023-11-28 20:41:43.588087 INFO::Fitting model to feature number 433, F454
## 2023-11-28 20:41:43.591904 INFO::Fitting model to feature number 434, F455
## 2023-11-28 20:41:43.595652 INFO::Fitting model to feature number 435, F456
## 2023-11-28 20:41:43.599382 INFO::Fitting model to feature number 436, F457
## 2023-11-28 20:41:43.602981 INFO::Fitting model to feature number 437, F458
## 2023-11-28 20:41:43.6065 INFO::Fitting model to feature number 438, F459
## 2023-11-28 20:41:43.610112 INFO::Fitting model to feature number 439, F461
## 2023-11-28 20:41:43.613635 INFO::Fitting model to feature number 440, F462
## 2023-11-28 20:41:43.617171 INFO::Fitting model to feature number 441, F463
## 2023-11-28 20:41:43.620815 INFO::Fitting model to feature number 442, F464
## 2023-11-28 20:41:43.624507 INFO::Fitting model to feature number 443, F465
## 2023-11-28 20:41:43.628274 INFO::Fitting model to feature number 444, F466
## 2023-11-28 20:41:43.631861 INFO::Fitting model to feature number 445, F467
## 2023-11-28 20:41:43.635459 INFO::Fitting model to feature number 446, F468
## 2023-11-28 20:41:43.639191 INFO::Fitting model to feature number 447, F469
## 2023-11-28 20:41:43.643044 INFO::Fitting model to feature number 448, F470
## 2023-11-28 20:41:43.64667 INFO::Fitting model to feature number 449, F471
## 2023-11-28 20:41:43.650265 INFO::Fitting model to feature number 450, F474
## 2023-11-28 20:41:43.653753 INFO::Fitting model to feature number 451, F475
## 2023-11-28 20:41:43.657359 INFO::Fitting model to feature number 452, F476
## 2023-11-28 20:41:43.660942 INFO::Fitting model to feature number 453, F477
## 2023-11-28 20:41:43.664495 INFO::Fitting model to feature number 454, F478
## 2023-11-28 20:41:43.668167 INFO::Fitting model to feature number 455, F479
## 2023-11-28 20:41:43.671833 INFO::Fitting model to feature number 456, F480
## 2023-11-28 20:41:43.675448 INFO::Fitting model to feature number 457, F481
## 2023-11-28 20:41:43.679101 INFO::Fitting model to feature number 458, F482
## 2023-11-28 20:41:43.682717 INFO::Fitting model to feature number 459, F483
## 2023-11-28 20:41:43.686311 INFO::Fitting model to feature number 460, F484
## 2023-11-28 20:41:43.689916 INFO::Fitting model to feature number 461, F485
## 2023-11-28 20:41:43.693528 INFO::Fitting model to feature number 462, F486
## 2023-11-28 20:41:43.697125 INFO::Fitting model to feature number 463, F487
## 2023-11-28 20:41:43.700695 INFO::Fitting model to feature number 464, F488
## 2023-11-28 20:41:43.7043 INFO::Fitting model to feature number 465, F489
## 2023-11-28 20:41:43.7082 INFO::Fitting model to feature number 466, F490
## 2023-11-28 20:41:43.711993 INFO::Fitting model to feature number 467, F491
## 2023-11-28 20:41:43.715671 INFO::Fitting model to feature number 468, F492
## 2023-11-28 20:41:43.71923 INFO::Fitting model to feature number 469, F493
## 2023-11-28 20:41:43.722821 INFO::Fitting model to feature number 470, F494
## 2023-11-28 20:41:43.726425 INFO::Fitting model to feature number 471, F495
## 2023-11-28 20:41:43.730062 INFO::Fitting model to feature number 472, F496
## 2023-11-28 20:41:43.733707 INFO::Fitting model to feature number 473, F497
## 2023-11-28 20:41:43.737324 INFO::Fitting model to feature number 474, F498
## 2023-11-28 20:41:43.740972 INFO::Fitting model to feature number 475, F499
## 2023-11-28 20:41:43.744619 INFO::Fitting model to feature number 476, F500
## 2023-11-28 20:41:43.74824 INFO::Fitting model to feature number 477, F501
## 2023-11-28 20:41:43.751764 INFO::Fitting model to feature number 478, F502
## 2023-11-28 20:41:43.755373 INFO::Fitting model to feature number 479, F503
## 2023-11-28 20:41:43.758972 INFO::Fitting model to feature number 480, F504
## 2023-11-28 20:41:43.76256 INFO::Fitting model to feature number 481, F505
## 2023-11-28 20:41:43.766431 INFO::Fitting model to feature number 482, F506
## 2023-11-28 20:41:43.770343 INFO::Fitting model to feature number 483, F507
## 2023-11-28 20:41:43.77409 INFO::Fitting model to feature number 484, F508
## 2023-11-28 20:41:43.777725 INFO::Fitting model to feature number 485, F509
## 2023-11-28 20:41:43.781363 INFO::Fitting model to feature number 486, F510
## 2023-11-28 20:41:43.784951 INFO::Fitting model to feature number 487, F511
## 2023-11-28 20:41:43.788622 INFO::Fitting model to feature number 488, F512
## 2023-11-28 20:41:43.792256 INFO::Fitting model to feature number 489, F513
## 2023-11-28 20:41:43.795903 INFO::Fitting model to feature number 490, F514
## 2023-11-28 20:41:43.799548 INFO::Fitting model to feature number 491, F515
## 2023-11-28 20:41:43.80318 INFO::Fitting model to feature number 492, F516
## 2023-11-28 20:41:43.806734 INFO::Fitting model to feature number 493, F517
## 2023-11-28 20:41:43.810378 INFO::Fitting model to feature number 494, F518
## 2023-11-28 20:41:43.814029 INFO::Fitting model to feature number 495, F519
## 2023-11-28 20:41:43.81762 INFO::Fitting model to feature number 496, F520
## 2023-11-28 20:41:43.82124 INFO::Fitting model to feature number 497, F521
## 2023-11-28 20:41:43.824832 INFO::Fitting model to feature number 498, F522
## 2023-11-28 20:41:43.828354 INFO::Fitting model to feature number 499, F523
## 2023-11-28 20:41:43.831818 INFO::Fitting model to feature number 500, F524
## 2023-11-28 20:41:43.835367 INFO::Fitting model to feature number 501, F525
## 2023-11-28 20:41:43.838982 INFO::Fitting model to feature number 502, F526
## 2023-11-28 20:41:43.842544 INFO::Fitting model to feature number 503, F527
## 2023-11-28 20:41:43.846094 INFO::Fitting model to feature number 504, F528
## 2023-11-28 20:41:43.849668 INFO::Fitting model to feature number 505, F529
## 2023-11-28 20:41:43.853264 INFO::Fitting model to feature number 506, F530
## 2023-11-28 20:41:43.856855 INFO::Fitting model to feature number 507, F531
## 2023-11-28 20:41:43.860443 INFO::Fitting model to feature number 508, F532
## 2023-11-28 20:41:43.86401 INFO::Fitting model to feature number 509, F533
## 2023-11-28 20:41:43.867642 INFO::Fitting model to feature number 510, F534
## 2023-11-28 20:41:43.871178 INFO::Fitting model to feature number 511, F535
## 2023-11-28 20:41:43.874675 INFO::Fitting model to feature number 512, F536
## 2023-11-28 20:41:43.87826 INFO::Fitting model to feature number 513, F537
## 2023-11-28 20:41:43.881839 INFO::Fitting model to feature number 514, F539
## 2023-11-28 20:41:43.885426 INFO::Fitting model to feature number 515, F540
## 2023-11-28 20:41:43.889025 INFO::Fitting model to feature number 516, F541
## 2023-11-28 20:41:43.892559 INFO::Fitting model to feature number 517, F543
## 2023-11-28 20:41:43.896163 INFO::Fitting model to feature number 518, F544
## 2023-11-28 20:41:43.89963 INFO::Fitting model to feature number 519, F545
## 2023-11-28 20:41:43.903166 INFO::Fitting model to feature number 520, F546
## 2023-11-28 20:41:43.906947 INFO::Fitting model to feature number 521, F547
## 2023-11-28 20:41:43.91058 INFO::Fitting model to feature number 522, F548
## 2023-11-28 20:41:43.914164 INFO::Fitting model to feature number 523, F549
## 2023-11-28 20:41:43.917733 INFO::Fitting model to feature number 524, F550
## 2023-11-28 20:41:43.921337 INFO::Fitting model to feature number 525, F551
## 2023-11-28 20:41:43.924911 INFO::Fitting model to feature number 526, F552
## 2023-11-28 20:41:43.928525 INFO::Fitting model to feature number 527, F553
## 2023-11-28 20:41:43.93218 INFO::Fitting model to feature number 528, F554
## 2023-11-28 20:41:43.935849 INFO::Fitting model to feature number 529, F555
## 2023-11-28 20:41:43.939496 INFO::Fitting model to feature number 530, F556
## 2023-11-28 20:41:43.943026 INFO::Fitting model to feature number 531, F557
## 2023-11-28 20:41:43.946707 INFO::Fitting model to feature number 532, F558
## 2023-11-28 20:41:43.950357 INFO::Fitting model to feature number 533, F559
## 2023-11-28 20:41:43.954004 INFO::Fitting model to feature number 534, F560
## 2023-11-28 20:41:43.957626 INFO::Fitting model to feature number 535, F561
## 2023-11-28 20:41:43.961214 INFO::Fitting model to feature number 536, F562
## 2023-11-28 20:41:43.96484 INFO::Fitting model to feature number 537, F563
## 2023-11-28 20:41:43.968435 INFO::Fitting model to feature number 538, F564
## 2023-11-28 20:41:43.972021 INFO::Fitting model to feature number 539, F566
## 2023-11-28 20:41:43.975634 INFO::Fitting model to feature number 540, F567
## 2023-11-28 20:41:43.97933 INFO::Fitting model to feature number 541, F568
## 2023-11-28 20:41:43.983033 INFO::Fitting model to feature number 542, F569
## 2023-11-28 20:41:43.98672 INFO::Fitting model to feature number 543, F570
## 2023-11-28 20:41:43.990376 INFO::Fitting model to feature number 544, F571
## 2023-11-28 20:41:43.99403 INFO::Fitting model to feature number 545, F572
## 2023-11-28 20:41:43.99778 INFO::Fitting model to feature number 546, F573
## 2023-11-28 20:41:44.001666 INFO::Fitting model to feature number 547, F574
## 2023-11-28 20:41:44.005313 INFO::Fitting model to feature number 548, F575
## 2023-11-28 20:41:44.008966 INFO::Fitting model to feature number 549, F576
## 2023-11-28 20:41:44.012652 INFO::Fitting model to feature number 550, F577
## 2023-11-28 20:41:44.01631 INFO::Fitting model to feature number 551, F578
## 2023-11-28 20:41:44.019951 INFO::Fitting model to feature number 552, F579
## 2023-11-28 20:41:44.023598 INFO::Fitting model to feature number 553, F580
## 2023-11-28 20:41:44.063112 INFO::Fitting model to feature number 554, F581
## 2023-11-28 20:41:44.066862 INFO::Fitting model to feature number 555, F582
## 2023-11-28 20:41:44.070474 INFO::Fitting model to feature number 556, F583
## 2023-11-28 20:41:44.074192 INFO::Fitting model to feature number 557, F584
## 2023-11-28 20:41:44.077853 INFO::Fitting model to feature number 558, F585
## 2023-11-28 20:41:44.081486 INFO::Fitting model to feature number 559, F586
## 2023-11-28 20:41:44.085135 INFO::Fitting model to feature number 560, F587
## 2023-11-28 20:41:44.088727 INFO::Fitting model to feature number 561, F588
## 2023-11-28 20:41:44.092337 INFO::Fitting model to feature number 562, F589
## 2023-11-28 20:41:44.095943 INFO::Fitting model to feature number 563, F590
## 2023-11-28 20:41:44.099502 INFO::Fitting model to feature number 564, F591
## 2023-11-28 20:41:44.10306 INFO::Fitting model to feature number 565, F592
## 2023-11-28 20:41:44.106555 INFO::Fitting model to feature number 566, F593
## 2023-11-28 20:41:44.110079 INFO::Fitting model to feature number 567, F594
## 2023-11-28 20:41:44.113603 INFO::Fitting model to feature number 568, F595
## 2023-11-28 20:41:44.11728 INFO::Fitting model to feature number 569, F596
## 2023-11-28 20:41:44.121141 INFO::Fitting model to feature number 570, F597
## 2023-11-28 20:41:44.124832 INFO::Fitting model to feature number 571, F598
## 2023-11-28 20:41:44.12838 INFO::Fitting model to feature number 572, F599
## 2023-11-28 20:41:44.13193 INFO::Fitting model to feature number 573, F600
## 2023-11-28 20:41:44.13545 INFO::Fitting model to feature number 574, F601
## 2023-11-28 20:41:44.13898 INFO::Fitting model to feature number 575, F602
## 2023-11-28 20:41:44.142689 INFO::Fitting model to feature number 576, F603
## 2023-11-28 20:41:44.146245 INFO::Fitting model to feature number 577, F605
## 2023-11-28 20:41:44.149803 INFO::Fitting model to feature number 578, F606
## 2023-11-28 20:41:44.153306 INFO::Fitting model to feature number 579, F607
## 2023-11-28 20:41:44.156874 INFO::Fitting model to feature number 580, F608
## 2023-11-28 20:41:44.160482 INFO::Fitting model to feature number 581, F609
## 2023-11-28 20:41:44.165381 INFO::Fitting model to feature number 582, F610
## 2023-11-28 20:41:44.169897 INFO::Fitting model to feature number 583, F611
## 2023-11-28 20:41:44.174179 INFO::Fitting model to feature number 584, F612
## 2023-11-28 20:41:44.178305 INFO::Fitting model to feature number 585, F613
## 2023-11-28 20:41:44.182167 INFO::Fitting model to feature number 586, F614
## 2023-11-28 20:41:44.185934 INFO::Fitting model to feature number 587, F615
## 2023-11-28 20:41:44.189637 INFO::Fitting model to feature number 588, F616
## 2023-11-28 20:41:44.193281 INFO::Fitting model to feature number 589, F617
## 2023-11-28 20:41:44.196973 INFO::Fitting model to feature number 590, F618
## 2023-11-28 20:41:44.200655 INFO::Fitting model to feature number 591, F619
## 2023-11-28 20:41:44.204348 INFO::Fitting model to feature number 592, F620
## 2023-11-28 20:41:44.208043 INFO::Fitting model to feature number 593, F621
## 2023-11-28 20:41:44.211736 INFO::Fitting model to feature number 594, F622
## 2023-11-28 20:41:44.215458 INFO::Fitting model to feature number 595, F623
## 2023-11-28 20:41:44.21921 INFO::Fitting model to feature number 596, F624
## 2023-11-28 20:41:44.222951 INFO::Fitting model to feature number 597, F625
## 2023-11-28 20:41:44.22671 INFO::Fitting model to feature number 598, F626
## 2023-11-28 20:41:44.230391 INFO::Fitting model to feature number 599, F627
## 2023-11-28 20:41:44.234091 INFO::Fitting model to feature number 600, F628
## 2023-11-28 20:41:44.237839 INFO::Fitting model to feature number 601, F629
## 2023-11-28 20:41:44.241877 INFO::Fitting model to feature number 602, F630
## 2023-11-28 20:41:44.245834 INFO::Fitting model to feature number 603, F631
## 2023-11-28 20:41:44.24963 INFO::Fitting model to feature number 604, F632
## 2023-11-28 20:41:44.253331 INFO::Fitting model to feature number 605, F633
## 2023-11-28 20:41:44.257047 INFO::Fitting model to feature number 606, F634
## 2023-11-28 20:41:44.260747 INFO::Fitting model to feature number 607, F635
## 2023-11-28 20:41:44.264413 INFO::Fitting model to feature number 608, F636
## 2023-11-28 20:41:44.268117 INFO::Fitting model to feature number 609, F637
## 2023-11-28 20:41:44.271813 INFO::Fitting model to feature number 610, F638
## 2023-11-28 20:41:44.275496 INFO::Fitting model to feature number 611, F639
## 2023-11-28 20:41:44.279238 INFO::Fitting model to feature number 612, F640
## 2023-11-28 20:41:44.282926 INFO::Fitting model to feature number 613, F641
## 2023-11-28 20:41:44.286625 INFO::Fitting model to feature number 614, F642
## 2023-11-28 20:41:44.290323 INFO::Fitting model to feature number 615, F643
## 2023-11-28 20:41:44.294005 INFO::Fitting model to feature number 616, F644
## 2023-11-28 20:41:44.297556 INFO::Fitting model to feature number 617, F645
## 2023-11-28 20:41:44.301061 INFO::Fitting model to feature number 618, F646
## 2023-11-28 20:41:44.304595 INFO::Fitting model to feature number 619, F647
## 2023-11-28 20:41:44.30818 INFO::Fitting model to feature number 620, F648
## 2023-11-28 20:41:44.311868 INFO::Fitting model to feature number 621, F649
## 2023-11-28 20:41:44.315608 INFO::Fitting model to feature number 622, F650
## 2023-11-28 20:41:44.319334 INFO::Fitting model to feature number 623, F651
## 2023-11-28 20:41:44.323072 INFO::Fitting model to feature number 624, F652
## 2023-11-28 20:41:44.326751 INFO::Fitting model to feature number 625, F653
## 2023-11-28 20:41:44.330443 INFO::Fitting model to feature number 626, F654
## 2023-11-28 20:41:44.334157 INFO::Fitting model to feature number 627, F655
## 2023-11-28 20:41:44.33786 INFO::Fitting model to feature number 628, F656
## 2023-11-28 20:41:44.341828 INFO::Fitting model to feature number 629, F657
## 2023-11-28 20:41:44.345806 INFO::Fitting model to feature number 630, F658
## 2023-11-28 20:41:44.349957 INFO::Fitting model to feature number 631, F659
## 2023-11-28 20:41:44.353929 INFO::Fitting model to feature number 632, F660
## 2023-11-28 20:41:44.357864 INFO::Fitting model to feature number 633, F661
## 2023-11-28 20:41:44.361616 INFO::Fitting model to feature number 634, F662
## 2023-11-28 20:41:44.365326 INFO::Fitting model to feature number 635, F663
## 2023-11-28 20:41:44.368989 INFO::Fitting model to feature number 636, F664
## 2023-11-28 20:41:44.372639 INFO::Fitting model to feature number 637, F665
## 2023-11-28 20:41:44.376161 INFO::Fitting model to feature number 638, F666
## 2023-11-28 20:41:44.379609 INFO::Fitting model to feature number 639, F667
## 2023-11-28 20:41:44.383078 INFO::Fitting model to feature number 640, F668
## 2023-11-28 20:41:44.386528 INFO::Fitting model to feature number 641, F669
## 2023-11-28 20:41:44.389989 INFO::Fitting model to feature number 642, F670
## 2023-11-28 20:41:44.393489 INFO::Fitting model to feature number 643, F671
## 2023-11-28 20:41:44.397 INFO::Fitting model to feature number 644, F672
## 2023-11-28 20:41:44.400466 INFO::Fitting model to feature number 645, F673
## 2023-11-28 20:41:44.403931 INFO::Fitting model to feature number 646, F674
## 2023-11-28 20:41:44.40741 INFO::Fitting model to feature number 647, F675
## 2023-11-28 20:41:44.410915 INFO::Fitting model to feature number 648, F676
## 2023-11-28 20:41:44.414382 INFO::Fitting model to feature number 649, F677
## 2023-11-28 20:41:44.417801 INFO::Fitting model to feature number 650, F678
## 2023-11-28 20:41:44.42127 INFO::Fitting model to feature number 651, F679
## 2023-11-28 20:41:44.424786 INFO::Fitting model to feature number 652, F680
## 2023-11-28 20:41:44.428472 INFO::Fitting model to feature number 653, F681
## 2023-11-28 20:41:44.432219 INFO::Fitting model to feature number 654, F682
## 2023-11-28 20:41:44.435981 INFO::Fitting model to feature number 655, F683
## 2023-11-28 20:41:44.439736 INFO::Fitting model to feature number 656, F684
## 2023-11-28 20:41:44.443503 INFO::Fitting model to feature number 657, F685
## 2023-11-28 20:41:44.447287 INFO::Fitting model to feature number 658, F686
## 2023-11-28 20:41:44.451017 INFO::Fitting model to feature number 659, F687
## 2023-11-28 20:41:44.454703 INFO::Fitting model to feature number 660, F688
## 2023-11-28 20:41:44.458377 INFO::Fitting model to feature number 661, F689
## 2023-11-28 20:41:44.462065 INFO::Fitting model to feature number 662, F690
## 2023-11-28 20:41:44.465742 INFO::Fitting model to feature number 663, F691
## 2023-11-28 20:41:44.469441 INFO::Fitting model to feature number 664, F692
## 2023-11-28 20:41:44.473133 INFO::Fitting model to feature number 665, F693
## 2023-11-28 20:41:44.477083 INFO::Fitting model to feature number 666, F694
## 2023-11-28 20:41:44.48093 INFO::Fitting model to feature number 667, F695
## 2023-11-28 20:41:44.484687 INFO::Fitting model to feature number 668, F696
## 2023-11-28 20:41:44.488415 INFO::Fitting model to feature number 669, F697
## 2023-11-28 20:41:44.492132 INFO::Fitting model to feature number 670, F698
## 2023-11-28 20:41:44.495858 INFO::Fitting model to feature number 671, F699
## 2023-11-28 20:41:44.4995 INFO::Fitting model to feature number 672, F700
## 2023-11-28 20:41:44.50318 INFO::Fitting model to feature number 673, F701
## 2023-11-28 20:41:44.506863 INFO::Fitting model to feature number 674, F702
## 2023-11-28 20:41:44.510577 INFO::Fitting model to feature number 675, F704
## 2023-11-28 20:41:44.514271 INFO::Fitting model to feature number 676, F705
## 2023-11-28 20:41:44.517992 INFO::Fitting model to feature number 677, F706
## 2023-11-28 20:41:44.521781 INFO::Fitting model to feature number 678, F707
## 2023-11-28 20:41:44.525482 INFO::Fitting model to feature number 679, F708
## 2023-11-28 20:41:44.529177 INFO::Fitting model to feature number 680, F709
## 2023-11-28 20:41:44.532888 INFO::Fitting model to feature number 681, F710
## 2023-11-28 20:41:44.536601 INFO::Fitting model to feature number 682, F711
## 2023-11-28 20:41:44.540318 INFO::Fitting model to feature number 683, F712
## 2023-11-28 20:41:44.544158 INFO::Fitting model to feature number 684, F713
## 2023-11-28 20:41:44.548142 INFO::Fitting model to feature number 685, F714
## 2023-11-28 20:41:44.551974 INFO::Fitting model to feature number 686, F715
## 2023-11-28 20:41:44.555731 INFO::Fitting model to feature number 687, F716
## 2023-11-28 20:41:44.559486 INFO::Fitting model to feature number 688, F717
## 2023-11-28 20:41:44.563285 INFO::Fitting model to feature number 689, F718
## 2023-11-28 20:41:44.567173 INFO::Fitting model to feature number 690, F719
## 2023-11-28 20:41:44.57091 INFO::Fitting model to feature number 691, F720
## 2023-11-28 20:41:44.574633 INFO::Fitting model to feature number 692, F721
## 2023-11-28 20:41:44.578257 INFO::Fitting model to feature number 693, F722
## 2023-11-28 20:41:44.581792 INFO::Fitting model to feature number 694, F723
## 2023-11-28 20:41:44.585349 INFO::Fitting model to feature number 695, F724
## 2023-11-28 20:41:44.588994 INFO::Fitting model to feature number 696, F725
## 2023-11-28 20:41:44.592753 INFO::Fitting model to feature number 697, F726
## 2023-11-28 20:41:44.596544 INFO::Fitting model to feature number 698, F727
## 2023-11-28 20:41:44.600376 INFO::Fitting model to feature number 699, F728
## 2023-11-28 20:41:44.604117 INFO::Fitting model to feature number 700, F729
## 2023-11-28 20:41:44.607784 INFO::Fitting model to feature number 701, F730
## 2023-11-28 20:41:44.611503 INFO::Fitting model to feature number 702, F731
## 2023-11-28 20:41:44.615158 INFO::Fitting model to feature number 703, F732
## 2023-11-28 20:41:44.618853 INFO::Fitting model to feature number 704, F733
## 2023-11-28 20:41:44.622562 INFO::Fitting model to feature number 705, F734
## 2023-11-28 20:41:44.62631 INFO::Fitting model to feature number 706, F735
## 2023-11-28 20:41:44.630202 INFO::Fitting model to feature number 707, F736
## 2023-11-28 20:41:44.634217 INFO::Fitting model to feature number 708, F737
## 2023-11-28 20:41:44.637953 INFO::Fitting model to feature number 709, F739
## 2023-11-28 20:41:44.641782 INFO::Fitting model to feature number 710, F740
## 2023-11-28 20:41:44.645568 INFO::Fitting model to feature number 711, F741
## 2023-11-28 20:41:44.649171 INFO::Fitting model to feature number 712, F742
## 2023-11-28 20:41:44.652726 INFO::Fitting model to feature number 713, F743
## 2023-11-28 20:41:44.656307 INFO::Fitting model to feature number 714, F744
## 2023-11-28 20:41:44.659905 INFO::Fitting model to feature number 715, F745
## 2023-11-28 20:41:44.663513 INFO::Fitting model to feature number 716, F746
## 2023-11-28 20:41:44.667111 INFO::Fitting model to feature number 717, F747
## 2023-11-28 20:41:44.670671 INFO::Fitting model to feature number 718, F748
## 2023-11-28 20:41:44.674346 INFO::Fitting model to feature number 719, F749
## 2023-11-28 20:41:44.67794 INFO::Fitting model to feature number 720, F750
## 2023-11-28 20:41:44.681479 INFO::Fitting model to feature number 721, F751
## 2023-11-28 20:41:44.685054 INFO::Fitting model to feature number 722, F752
## 2023-11-28 20:41:44.68868 INFO::Fitting model to feature number 723, F753
## 2023-11-28 20:41:44.6924 INFO::Fitting model to feature number 724, F754
## 2023-11-28 20:41:44.696034 INFO::Fitting model to feature number 725, F755
## 2023-11-28 20:41:44.699634 INFO::Fitting model to feature number 726, F756
## 2023-11-28 20:41:44.703406 INFO::Fitting model to feature number 727, F757
## 2023-11-28 20:41:44.707221 INFO::Fitting model to feature number 728, F758
## 2023-11-28 20:41:44.711031 INFO::Fitting model to feature number 729, F759
## 2023-11-28 20:41:44.714897 INFO::Fitting model to feature number 730, F760
## 2023-11-28 20:41:44.71864 INFO::Fitting model to feature number 731, F761
## 2023-11-28 20:41:44.722417 INFO::Fitting model to feature number 732, F762
## 2023-11-28 20:41:44.726183 INFO::Fitting model to feature number 733, F763
## 2023-11-28 20:41:44.729981 INFO::Fitting model to feature number 734, F764
## 2023-11-28 20:41:44.733753 INFO::Fitting model to feature number 735, F765
## 2023-11-28 20:41:44.737499 INFO::Fitting model to feature number 736, F766
## 2023-11-28 20:41:44.741315 INFO::Fitting model to feature number 737, F767
## 2023-11-28 20:41:44.745078 INFO::Fitting model to feature number 738, F768
## 2023-11-28 20:41:44.748826 INFO::Fitting model to feature number 739, F769
## 2023-11-28 20:41:44.753999 INFO::Fitting model to feature number 740, F770
## 2023-11-28 20:41:44.758497 INFO::Fitting model to feature number 741, F771
## 2023-11-28 20:41:44.762668 INFO::Fitting model to feature number 742, F772
## 2023-11-28 20:41:44.766737 INFO::Fitting model to feature number 743, F773
## 2023-11-28 20:41:44.770706 INFO::Fitting model to feature number 744, F774
## 2023-11-28 20:41:44.77473 INFO::Fitting model to feature number 745, F775
## 2023-11-28 20:41:44.778663 INFO::Fitting model to feature number 746, F776
## 2023-11-28 20:41:44.782592 INFO::Fitting model to feature number 747, F777
## 2023-11-28 20:41:44.786498 INFO::Fitting model to feature number 748, F778
## 2023-11-28 20:41:44.790515 INFO::Fitting model to feature number 749, F779
## 2023-11-28 20:41:44.794429 INFO::Fitting model to feature number 750, F780
## 2023-11-28 20:41:44.798364 INFO::Fitting model to feature number 751, F781
## 2023-11-28 20:41:44.802288 INFO::Fitting model to feature number 752, F782
## 2023-11-28 20:41:44.806085 INFO::Fitting model to feature number 753, F783
## 2023-11-28 20:41:44.809947 INFO::Fitting model to feature number 754, F784
## 2023-11-28 20:41:44.813798 INFO::Fitting model to feature number 755, F785
## 2023-11-28 20:41:44.817609 INFO::Fitting model to feature number 756, F786
## 2023-11-28 20:41:44.821417 INFO::Fitting model to feature number 757, F787
## 2023-11-28 20:41:44.825255 INFO::Fitting model to feature number 758, F788
## 2023-11-28 20:41:44.829334 INFO::Fitting model to feature number 759, F789
## 2023-11-28 20:41:44.833208 INFO::Fitting model to feature number 760, F790
## 2023-11-28 20:41:44.836925 INFO::Fitting model to feature number 761, F791
## 2023-11-28 20:41:44.840636 INFO::Fitting model to feature number 762, F792
## 2023-11-28 20:41:44.844364 INFO::Fitting model to feature number 763, F793
## 2023-11-28 20:41:44.848039 INFO::Fitting model to feature number 764, F794
## 2023-11-28 20:41:44.851726 INFO::Fitting model to feature number 765, F795
## 2023-11-28 20:41:44.85546 INFO::Fitting model to feature number 766, F796
## 2023-11-28 20:41:44.859256 INFO::Fitting model to feature number 767, F797
## 2023-11-28 20:41:44.863037 INFO::Fitting model to feature number 768, F798
## 2023-11-28 20:41:44.866801 INFO::Fitting model to feature number 769, F799
## 2023-11-28 20:41:44.870528 INFO::Fitting model to feature number 770, F800
## 2023-11-28 20:41:44.874319 INFO::Fitting model to feature number 771, F801
## 2023-11-28 20:41:44.878044 INFO::Fitting model to feature number 772, F802
## 2023-11-28 20:41:44.881579 INFO::Fitting model to feature number 773, F803
## 2023-11-28 20:41:44.885144 INFO::Fitting model to feature number 774, F804
## 2023-11-28 20:41:44.88872 INFO::Fitting model to feature number 775, F805
## 2023-11-28 20:41:44.892363 INFO::Fitting model to feature number 776, F806
## 2023-11-28 20:41:44.895892 INFO::Fitting model to feature number 777, F808
## 2023-11-28 20:41:44.899542 INFO::Fitting model to feature number 778, F809
## 2023-11-28 20:41:44.903301 INFO::Fitting model to feature number 779, F810
## 2023-11-28 20:41:44.907058 INFO::Fitting model to feature number 780, F811
## 2023-11-28 20:41:44.910787 INFO::Fitting model to feature number 781, F812
## 2023-11-28 20:41:44.91457 INFO::Fitting model to feature number 782, F813
## 2023-11-28 20:41:44.918313 INFO::Fitting model to feature number 783, F814
## 2023-11-28 20:41:44.922182 INFO::Fitting model to feature number 784, F815
## 2023-11-28 20:41:44.926244 INFO::Fitting model to feature number 785, F816
## 2023-11-28 20:41:44.930271 INFO::Fitting model to feature number 786, F817
## 2023-11-28 20:41:44.934308 INFO::Fitting model to feature number 787, F818
## 2023-11-28 20:41:44.938418 INFO::Fitting model to feature number 788, F819
## 2023-11-28 20:41:44.9424 INFO::Fitting model to feature number 789, F820
## 2023-11-28 20:41:44.946253 INFO::Fitting model to feature number 790, F821
## 2023-11-28 20:41:44.950019 INFO::Fitting model to feature number 791, F822
## 2023-11-28 20:41:44.953794 INFO::Fitting model to feature number 792, F823
## 2023-11-28 20:41:44.957569 INFO::Fitting model to feature number 793, F824
## 2023-11-28 20:41:44.961478 INFO::Fitting model to feature number 794, F825
## 2023-11-28 20:41:45.002257 INFO::Fitting model to feature number 795, F826
## 2023-11-28 20:41:45.006399 INFO::Fitting model to feature number 796, F827
## 2023-11-28 20:41:45.010186 INFO::Fitting model to feature number 797, F828
## 2023-11-28 20:41:45.013926 INFO::Fitting model to feature number 798, F829
## 2023-11-28 20:41:45.0177 INFO::Fitting model to feature number 799, F830
## 2023-11-28 20:41:45.021466 INFO::Fitting model to feature number 800, F831
## 2023-11-28 20:41:45.025291 INFO::Fitting model to feature number 801, F832
## 2023-11-28 20:41:45.029073 INFO::Fitting model to feature number 802, F833
## 2023-11-28 20:41:45.032777 INFO::Fitting model to feature number 803, F834
## 2023-11-28 20:41:45.036621 INFO::Fitting model to feature number 804, F835
## 2023-11-28 20:41:45.040433 INFO::Fitting model to feature number 805, F836
## 2023-11-28 20:41:45.04417 INFO::Fitting model to feature number 806, F837
## 2023-11-28 20:41:45.047891 INFO::Fitting model to feature number 807, F838
## 2023-11-28 20:41:45.051611 INFO::Fitting model to feature number 808, F839
## 2023-11-28 20:41:45.05536 INFO::Fitting model to feature number 809, F840
## 2023-11-28 20:41:45.059077 INFO::Fitting model to feature number 810, F841
## 2023-11-28 20:41:45.062834 INFO::Fitting model to feature number 811, F842
## 2023-11-28 20:41:45.066674 INFO::Fitting model to feature number 812, F843
## 2023-11-28 20:41:45.070633 INFO::Fitting model to feature number 813, F844
## 2023-11-28 20:41:45.074615 INFO::Fitting model to feature number 814, F845
## 2023-11-28 20:41:45.07857 INFO::Fitting model to feature number 815, F846
## 2023-11-28 20:41:45.082531 INFO::Fitting model to feature number 816, F847
## 2023-11-28 20:41:45.086631 INFO::Fitting model to feature number 817, F848
## 2023-11-28 20:41:45.091001 INFO::Fitting model to feature number 818, F849
## 2023-11-28 20:41:45.094989 INFO::Fitting model to feature number 819, F850
## 2023-11-28 20:41:45.09877 INFO::Fitting model to feature number 820, F851
## 2023-11-28 20:41:45.102446 INFO::Fitting model to feature number 821, F852
## 2023-11-28 20:41:45.106096 INFO::Fitting model to feature number 822, F853
## 2023-11-28 20:41:45.109823 INFO::Fitting model to feature number 823, F854
## 2023-11-28 20:41:45.113599 INFO::Fitting model to feature number 824, F855
## 2023-11-28 20:41:45.117325 INFO::Fitting model to feature number 825, F856
## 2023-11-28 20:41:45.120926 INFO::Fitting model to feature number 826, F857
## 2023-11-28 20:41:45.124499 INFO::Fitting model to feature number 827, F858
## 2023-11-28 20:41:45.128116 INFO::Fitting model to feature number 828, F859
## 2023-11-28 20:41:45.132893 INFO::Fitting model to feature number 829, F860
## 2023-11-28 20:41:45.136922 INFO::Fitting model to feature number 830, F861
## 2023-11-28 20:41:45.140836 INFO::Fitting model to feature number 831, F862
## 2023-11-28 20:41:45.144572 INFO::Fitting model to feature number 832, F863
## 2023-11-28 20:41:45.148212 INFO::Fitting model to feature number 833, F864
## 2023-11-28 20:41:45.151995 INFO::Fitting model to feature number 834, F865
## 2023-11-28 20:41:45.156155 INFO::Fitting model to feature number 835, F866
## 2023-11-28 20:41:45.160781 INFO::Fitting model to feature number 836, F867
## 2023-11-28 20:41:45.164938 INFO::Fitting model to feature number 837, F868
## 2023-11-28 20:41:45.168692 INFO::Fitting model to feature number 838, F869
## 2023-11-28 20:41:45.172401 INFO::Fitting model to feature number 839, F870
## 2023-11-28 20:41:45.176063 INFO::Fitting model to feature number 840, F871
## 2023-11-28 20:41:45.179763 INFO::Fitting model to feature number 841, F872
## 2023-11-28 20:41:45.18342 INFO::Fitting model to feature number 842, F873
## 2023-11-28 20:41:45.187125 INFO::Fitting model to feature number 843, F874
## 2023-11-28 20:41:45.190754 INFO::Fitting model to feature number 844, F875
## 2023-11-28 20:41:45.194503 INFO::Fitting model to feature number 845, F876
## 2023-11-28 20:41:45.198498 INFO::Fitting model to feature number 846, F877
## 2023-11-28 20:41:45.202319 INFO::Fitting model to feature number 847, F878
## 2023-11-28 20:41:45.206059 INFO::Fitting model to feature number 848, F879
## 2023-11-28 20:41:45.210048 INFO::Fitting model to feature number 849, F880
## 2023-11-28 20:41:45.213919 INFO::Fitting model to feature number 850, F881
## 2023-11-28 20:41:45.217811 INFO::Fitting model to feature number 851, F882
## 2023-11-28 20:41:45.224068 INFO::Fitting model to feature number 852, F883
## 2023-11-28 20:41:45.228427 INFO::Fitting model to feature number 853, F884
## 2023-11-28 20:41:45.23252 INFO::Fitting model to feature number 854, F885
## 2023-11-28 20:41:45.236557 INFO::Fitting model to feature number 855, F886
## 2023-11-28 20:41:45.242218 INFO::Fitting model to feature number 856, F887
## 2023-11-28 20:41:45.246571 INFO::Fitting model to feature number 857, F888
## 2023-11-28 20:41:45.251018 INFO::Fitting model to feature number 858, F889
## 2023-11-28 20:41:45.25519 INFO::Fitting model to feature number 859, F890
## 2023-11-28 20:41:45.259149 INFO::Fitting model to feature number 860, F891
## 2023-11-28 20:41:45.263585 INFO::Fitting model to feature number 861, F892
## 2023-11-28 20:41:45.267304 INFO::Fitting model to feature number 862, F893
## 2023-11-28 20:41:45.27107 INFO::Fitting model to feature number 863, F894
## 2023-11-28 20:41:45.274842 INFO::Fitting model to feature number 864, F895
## 2023-11-28 20:41:45.27852 INFO::Fitting model to feature number 865, F896
## 2023-11-28 20:41:45.282228 INFO::Fitting model to feature number 866, F897
## 2023-11-28 20:41:45.286104 INFO::Fitting model to feature number 867, F898
## 2023-11-28 20:41:45.289963 INFO::Fitting model to feature number 868, F899
## 2023-11-28 20:41:45.293866 INFO::Fitting model to feature number 869, F900
## 2023-11-28 20:41:45.485197 INFO::Counting total values for each feature
## 2023-11-28 20:41:45.619412 INFO::Writing filtered data to file Macarron_output/maaslin2_results/features/filtered_data.tsv
## 2023-11-28 20:41:45.767886 INFO::Writing filtered, normalized data to file Macarron_output/maaslin2_results/features/filtered_data_norm.tsv
## 2023-11-28 20:41:45.956339 INFO::Writing filtered, normalized, transformed data to file Macarron_output/maaslin2_results/features/filtered_data_norm_transformed.tsv
## 2023-11-28 20:41:46.098965 INFO::Writing residuals to file Macarron_output/maaslin2_results/fits/residuals.rds
## 2023-11-28 20:41:46.170161 INFO::Writing fitted values to file Macarron_output/maaslin2_results/fits/fitted.rds
## 2023-11-28 20:41:46.228504 INFO::Writing all results to file (ordered by increasing q-values): Macarron_output/maaslin2_results/all_results.tsv
## 2023-11-28 20:41:46.256121 INFO::Writing the significant results (those which are less than or equal to the threshold of 0.250000 ) to file (ordered by increasing q-values): Macarron_output/maaslin2_results/significant_results.tsv
## 2023-11-28 20:41:46.268864 INFO::Writing heatmap of significant results to file: Macarron_output/maaslin2_results/heatmap.pdf
## Initiating effect size calculations
## Calculating mean abundance in: IBD
## Calculating mean abundance in: Control
## Calculating effect size in: IBD
## Initiating prioritization
## Calculating meta-rank and prioritizing metabolic features
## 2023-11-28 20:41:46.775005 INFO::Writing all prioritized metabolites to file: Macarron_output/prioritized_metabolites_all.csv
## 2023-11-28 20:41:46.787826 INFO::Writing characterizable prioritized metabolites to file: Macarron_output/prioritized_metabolites_characterizable.csv
## 2023-11-28 20:41:46.814525 INFO::Writing highly prioritized metabolites in IBD to file: Macarron_output/highly_prioritized_per_module_in_IBD.csv
abundances_df = read.csv(file = prism_abundances, row.names = 1) # setting features as rownames
annotations_df = read.csv(file = prism_annotations, row.names = 1) # setting features as rownames
metadata_df = read.csv(file = prism_metadata, row.names = 1) # setting samples as rownames
taxonomy_df = read.csv(file = mets_taxonomy)
# Running Macarron
prism_prioritized <- Macarron::Macarron(input_abundances = abundances_df,
input_annotations = annotations_df,
input_metadata = metadata_df,
input_taxonomy = taxonomy_df)
The Macarron::Macarron()
function is a wrapper for the Macarron framework. Users can also apply individual functions on the input dataframes to achieve same results as the wrapper with the added benefit of storing output from each function for other analyses. There are seven steps:
# Step 1: Storing input data in a summarized experiment object
prism_mbx <- prepInput(input_abundances = abundances_df,
input_annotations = annotations_df,
input_metadata = metadata_df)
# Step 2: Creating a distance matrix from pairwise correlations in abundances of metabolic features
prism_w <- makeDisMat(se = prism_mbx)
# Step 3: Finding covariance modules
prism_modules <- findMacMod(se = prism_mbx,
w = prism_w,
input_taxonomy = taxonomy_df)
# The output is a list containing two dataframes- module assignments and measures of success
# if evaluateMOS=TRUE. To write modules to a separate dataframe, do:
prism_module_assignments <- prism_modules[[1]]
prism_modules_mos <- prism_modules[[2]]
# Step 4: Calculating AVA
prism_ava <- calAVA(se = prism_mbx,
mod.assn = prism_modules)
# Step 5: Calculating q-value
prism_qval <- calQval(se = prism_mbx,
mod.assn = prism_modules)
# Step 6: Calculating effect size
prism_es <- calES(se = prism_mbx,
mac.qval = prism_qval)
# Step 7: Prioritizing metabolic features
prism_prioritized <- prioritize(se = prism_mbx,
mod.assn = prism_modules,
mac.ava = prism_ava,
mac.qval = prism_qval,
mac.es = prism_es)
# The output is a list containing two dataframes- all prioritized metabolic features and
# only characterizable metabolic features.
all_prioritized <- prism_prioritized[[1]]
char_prioritized <- prism_prioritized[[2]]
# Step 8 (optional): View only the highly prioritized metabolic features in each module
prism_highly_prioritized <- showBest(prism_prioritized)
Session info from running the demo in R can be displayed with the following command.
sessionInfo()
## R version 4.3.2 (2023-10-31)
## Platform: aarch64-apple-darwin20 (64-bit)
## Running under: macOS Ventura 13.6.1
##
## Matrix products: default
## BLAS: /Library/Frameworks/R.framework/Versions/4.3-arm64/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.3-arm64/Resources/lib/libRlapack.dylib; LAPACK version 3.11.0
##
## locale:
## [1] C/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
##
## time zone: America/New_York
## tzcode source: internal
##
## attached base packages:
## [1] stats4 stats graphics grDevices utils datasets methods
## [8] base
##
## other attached packages:
## [1] Macarron_1.6.0 SummarizedExperiment_1.32.0
## [3] Biobase_2.62.0 GenomicRanges_1.54.1
## [5] GenomeInfoDb_1.38.1 IRanges_2.36.0
## [7] S4Vectors_0.40.2 BiocGenerics_0.48.1
## [9] MatrixGenerics_1.14.0 matrixStats_1.0.0
## [11] BiocStyle_2.30.0
##
## loaded via a namespace (and not attached):
## [1] mnormt_2.1.1 DBI_1.1.3 bitops_1.0-7
## [4] pbapply_1.7-2 gridExtra_2.3 rlang_1.1.1
## [7] magrittr_2.0.3 compiler_4.3.2 RSQLite_2.3.2
## [10] png_0.1-8 vctrs_0.6.4 stringr_1.5.0
## [13] pkgconfig_2.0.3 crayon_1.5.2 fastmap_1.1.1
## [16] backports_1.4.1 XVector_0.42.0 utf8_1.2.4
## [19] rmarkdown_2.25 preprocessCore_1.64.0 bit_4.0.5
## [22] xfun_0.41 zlibbioc_1.48.0 cachem_1.0.8
## [25] jsonlite_1.8.7 blob_1.2.4 DelayedArray_0.28.0
## [28] BiocParallel_1.36.0 psych_2.3.9 Maaslin2_1.16.0
## [31] parallel_4.3.2 cluster_2.1.4 biglm_0.9-2.1
## [34] R6_2.5.1 RColorBrewer_1.1-3 stringi_1.7.12
## [37] bslib_0.5.1 rpart_4.1.21 jquerylib_0.1.4
## [40] Rcpp_1.0.11 bookdown_0.36 iterators_1.0.14
## [43] knitr_1.45 WGCNA_1.72-1 base64enc_0.1-3
## [46] Matrix_1.6-1.1 splines_4.3.2 nnet_7.3-19
## [49] tidyselect_1.2.0 rstudioapi_0.15.0 abind_1.4-5
## [52] yaml_2.3.7 doParallel_1.0.17 codetools_0.2-19
## [55] plyr_1.8.9 lattice_0.22-5 tibble_3.2.1
## [58] withr_2.5.2 KEGGREST_1.42.0 evaluate_0.23
## [61] foreign_0.8-85 survival_3.5-7 getopt_1.20.4
## [64] Biostrings_2.70.1 pillar_1.9.0 BiocManager_1.30.22
## [67] checkmate_2.3.0 foreach_1.5.2 pcaPP_2.0-3
## [70] generics_0.1.3 RCurl_1.98-1.13 ggplot2_3.4.4
## [73] munsell_0.5.0 scales_1.2.1 glue_1.6.2
## [76] pheatmap_1.0.12 Hmisc_5.1-1 tools_4.3.2
## [79] robustbase_0.99-0 data.table_1.14.8 mvtnorm_1.2-3
## [82] fastcluster_1.2.3 grid_4.3.2 optparse_1.7.3
## [85] impute_1.76.0 AnnotationDbi_1.64.1 colorspace_2.1-0
## [88] nlme_3.1-163 GenomeInfoDbData_1.2.11 htmlTable_2.4.2
## [91] Formula_1.2-5 cli_3.6.1 fansi_1.0.5
## [94] S4Arrays_1.2.0 dplyr_1.1.3 DEoptimR_1.1-3
## [97] gtable_0.3.4 hash_2.2.6.3 logging_0.10-108
## [100] dynamicTreeCut_1.63-1 sass_0.4.7 digest_0.6.33
## [103] SparseArray_1.2.2 htmlwidgets_1.6.2 memoise_2.0.1
## [106] htmltools_0.5.7 lifecycle_1.0.3 httr_1.4.7
## [109] GO.db_3.18.0 bit64_4.0.5
The input taxonomy dataframe can be generated using the input metabolic features annotation dataframe using Macarron::decorateID()
. This function annotates an HMDB ID or a PubChem CID with the chemical class and subclass of the metabolite.
taxonomy_df <- decorateID(input_annotations = annotations_df)
write.csv(taxonomy_df, file="demo_taxonomy.csv", row.names = FALSE)
A record of all chosen parameters and steps that were followed during execution.
This file provides information about the properties of covariance modules used in the analysis. By default, modules are generated using a minimum module size (MMS) (argument: min_module_size
) equal to cube root of the total number of prevalent metabolic features. Macarron evaluates 9 measures of success (MOS) that collectively capture the “correctness” and chemical homogeneity of the modules. The MOS are as follows:
This folder contains the Maaslin2 log file (maaslin2.log), significant associations found by Maaslin2 (significant_results.tsv) and the linear model residuals file (residuals.rds). For more information, see Maaslin2.
Ideally, at least 50% metabolic features must be retained after prevalence filtering. By default, Macarron uses the union of metabolic features observed (non-zero abundance) in at least 70% samples of any phenotype for further analysis. This prevalence threshold may be high for some metabolomics datasets and can be changed using the min_prevalence
argument.
prism_prioritized <- Macarron::Macarron(input_abundances = abundances_df,
input_annotations = annotations_df,
input_metadata = metadata_df,
input_taxonomy = taxonomy_df,
min_prevalence = 0.5)
# or
prism_w <- makeDisMat(se = prism_mbx,
min_prevalence = 0.5)
By default, cube root of the total number of prevalent features is used as the minimum module size (MMS) (argument: min_module_size
) for module detection and generation. We expect this to work for most real world datasets. To determine if the modules are optimal for further analysis, Macarron evaluates several measures of success (MOS) as described above. In addition to evaluating MOS for modules generated using the default MMS, Macarron also evaluates MOS for MMS values that are larger (MMS+5, MMS+10) and smaller (MMS-5, MMS-10) than the default MMS. If you find that the MOS improve with larger or smaller MMS, you may change the default accordingly. For more details about module detection, please see WGCNA
and dynamicTreeCut
.
# See MOS of modules generated using default
prism_modules <- findMacMod(se = prism_mbx,
w = prism_w,
input_taxonomy = taxonomy_df)
prism_modules_mos <- prism_modules[[2]]
View(prism_modules_mos)
# Change MMS
prism_modules <- findMacMod(se = prism_mbx,
w = prism_w,
input_taxonomy = taxonomy_df,
min_module_size = 10)
Macarron uses Maaslin2 for determining the q-value of differential abundance in a phenotype of interest. For default execution, the phenotype of interest must be a category in column 1 of the metadata dataframe e.g. IBD in diagnosis in the demo. This is also the column that is picked by the metadata_variable
argument for identifying the main phenotypes/conditions in any dataset (see Macarron.log file). Further, in the default execution, all columns in the metadata table are considered as fixed effects and the alphabetically first categorical variable in each covariate with two categories is considered as the reference. Maaslin2 requires reference categories to be explicitly defined for all categorical metadata with more than two categories.
Defaults can be changed with the arguments fixed_effects
, random_effects
and reference
. In the demo example, fixed effects
and reference
can be defined as follows:
prism_qval <- calQval(se = prism_mbx,
mod.assn = prism_modules,
metadata_variable = "diagnosis",
fixed_effects = c("diagnosis","age","antibiotics"),
reference = c("diagnosis,Control";"antibiotics,No"))
The package source contains a script MacarronCMD.R
in inst/scripts
to invoke Macarron in the command line using Rscript.
The inst/scripts
folder also contains a README file that comprehensively documents the usage of the script.