1 Introduction

This vignette will illustrate how the SomaScan.db package can be used to extend the results of basic bioinformatic analyses performed on SomaScan data. In this vignette, we will use tools from SomaDataIO, in conjunction with SomaScan.db, to identify and annotate proteins (and ultimately, genes and their biological pathways) that are associated with a clinical variable of interest; e.g. Age.

This workflow assumes the user has a basic knowledge of the R programming language. In addition, it is assumed that the user is familiar with the ADAT format, as well as the documentation in SomaDataIO and the SomaLogic-Data Github repository. For more information about the ADAT format, as well as a detailed description of the fields found in an ADAT, please reference the SomaLogic-Data repository README.

library(dplyr)
library(GO.db)
library(SomaDataIO)
library(SomaScan.db)

2 Reading an ADAT

The ADAT file format is a SomaLogic-specific, tab-delimited text file designed to store SomaScan study data. The example ADAT file used for this walkthrough, example_data10.adat, contains a SomaScan 5k study from a set of 10 human samples. The measurements and identifiers have been altered to protect personally identifiable information (PII), while retaining the underlying biological signal as much as possible.

To begin, we will utilize SomaDataIO::read_adat() to load the example ADAT file:

# Retrieve the example ADAT file from the SomaDataIO package
file <- system.file("extdata", "example_data10.adat",
                    package = "SomaDataIO", mustWork = TRUE
)
# Read in the file
adat <- SomaDataIO::read_adat(file)

adat
## ══ SomaScan Data ═══════════════════════════════════════════════════════════════
##      SomaScan version     V4 (5k)
##      Signal Space         5k
##      Attributes intact    ✓
##      Rows                 10
##      Columns              5318
##      Clinical Data        34
##      Features             5284
## ── Column Meta ─────────────────────────────────────────────────────────────────
## ℹ SeqId, SeqIdVersion, SomaId, TargetFullName, Target, UniProt, EntrezGeneID,
## ℹ EntrezGeneSymbol, Organism, Units, Type, Dilution, PlateScale_Reference,
## ℹ CalReference, Cal_Example_Adat_Set001, ColCheck,
## ℹ CalQcRatio_Example_Adat_Set001_170255, QcReference_170255,
## ℹ Cal_Example_Adat_Set002, CalQcRatio_Example_Adat_Set002_170255, Dilution2
## ── Tibble ──────────────────────────────────────────────────────────────────────
## # A tibble: 10 × 5,319
##    row_names      PlateId  PlateRunDate ScannerID PlatePosition SlideId Subarray
##    <chr>          <chr>    <chr>        <chr>     <chr>           <dbl>    <dbl>
##  1 258495800012_3 Example… 2020-06-18   SG152144… H9            2.58e11        3
##  2 258495800004_7 Example… 2020-06-18   SG152144… H8            2.58e11        7
##  3 258495800010_8 Example… 2020-06-18   SG152144… H7            2.58e11        8
##  4 258495800003_4 Example… 2020-06-18   SG152144… H6            2.58e11        4
##  5 258495800009_4 Example… 2020-06-18   SG152144… H5            2.58e11        4
##  6 258495800012_8 Example… 2020-06-18   SG152144… H4            2.58e11        8
##  7 258495800001_3 Example… 2020-06-18   SG152144… H3            2.58e11        3
##  8 258495800004_8 Example… 2020-06-18   SG152144… H2            2.58e11        8
##  9 258495800001_8 Example… 2020-06-18   SG152144… H12           2.58e11        8
## 10 258495800004_3 Example… 2020-06-18   SG152144… H11           2.58e11        3
## # ℹ 5,312 more variables: SampleId <chr>, SampleType <chr>,
## #   PercentDilution <int>, SampleMatrix <chr>, Barcode <lgl>, Barcode2d <chr>,
## #   SampleName <lgl>, SampleNotes <lgl>, AliquotingNotes <lgl>,
## #   SampleDescription <chr>, …
## ════════════════════════════════════════════════════════════════════════════════

2.1 Data Prep and Exploration

Next, we will perform some preliminary data exploration of our variable of interest (Age):

summary(adat$Age)
##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
##   36.00   41.00   55.00   55.78   71.00   77.00       1
hist(adat$Age,
     xlab = "Age (years)",
     main = "Age Distribution"
)

The subjects in this example data set are all adults, with age ranging from 36 to 77 years.

However, as suggested by the summary table above, there is 1 patient that is missing age information:

dplyr::filter(adat, is.na(Sex)) %>%
    dplyr::select(SlideId, Age)
## ══ SomaScan Data ═══════════════════════════════════════════════════════════════
##      SomaScan version     V4 (5k)
##      Signal Space         5k
##      Attributes intact    ✓
##      Rows                 1
##      Columns              2
##      Clinical Data        2
##      Features             0
## ── Column Meta ─────────────────────────────────────────────────────────────────
## ℹ SeqId, SeqIdVersion, SomaId, TargetFullName, Target, UniProt, EntrezGeneID,
## ℹ EntrezGeneSymbol, Organism, Units, Type, Dilution, PlateScale_Reference,
## ℹ CalReference, Cal_Example_Adat_Set001, ColCheck,
## ℹ CalQcRatio_Example_Adat_Set001_170255, QcReference_170255,
## ℹ Cal_Example_Adat_Set002, CalQcRatio_Example_Adat_Set002_170255, Dilution2
## ── Tibble ──────────────────────────────────────────────────────────────────────
## # A tibble: 1 × 3
##   row_names           SlideId   Age
##   <chr>                 <dbl> <int>
## 1 258495800004_3 258495800004    NA
## ════════════════════════════════════════════════════════════════════════════════

Note: You may notice that the select function above has the namespace (dplyr) specified; this is to distinguish between dplyr::select() and SomaScan.db::select(), both of which will be used in this vignette. A more thorough explanation of why this is important can be found in the “select namespace collision” section.

Samples corresponding to this patient will need to be removed before proceeding:

adat <- dplyr::filter(adat, !is.na(Age))

As a quick sanity check: this ADAT was generated using the 5k SomaScan assay menu, which indicates that there should be RFU values for approximately 5,000 analytes.

analytes <- SomaDataIO::getAnalytes(adat)

head(analytes)
## [1] "seq.10000.28" "seq.10001.7"  "seq.10003.15" "seq.10006.25" "seq.10008.43"
## [6] "seq.10011.65"
length(analytes)
## [1] 5284

Indeed, there are 5284 analytes in this example ADAT file, consistent with the assay version.


2.2 Note on SeqId format

The values obtained in analytes above contains the same information as a SomaLogic SeqId, just converted to a more R-friendly format (i.e. the seq-prefix and "." delimiters). This format of identifier is used throughout SomaDataIO, and is also compatible with SomaScan.db. Values obtained from SomaDataIO (with the seq-prefix) are converted to SeqIds automatically when used by methods in SomaScan.db.

3 Identifying Associations

We can now examine the data to see if any analytes are correlated with the variable Age. First, however, the data be be pre-processed. SomaLogic generally recommends to log-transform the RFU values in an ADAT prior to analysis.

log10_adat <- log10(adat)

After log-transformation, we can examine the correlations and identify analytes that are positively correlated with Age. Here, correlations will be calculated using stats::cor.test():

# Calculate correlations for each analyte
cors_df <- lapply(analytes, function(x) {
    results <- stats::cor.test(log10_adat$Age, log10_adat[[x]],
                               method = "spearman", exact = FALSE)
    results <- results[c("estimate", "p.value")]
    unlist(results)
}) %>% setNames(analytes)

# Bind results together into a single dataframe
cors_df <- dplyr::bind_rows(cors_df, .id = "analytes")

# Isolate top positive correlations
top_posCor <- cors_df %>%
    dplyr::filter(p.value < 0.05) %>% # Retain significant cors only
    dplyr::filter(estimate.rho >= 0.75) %>% # Retain strong correlations
    arrange(desc(estimate.rho))

nrow(top_posCor)
## [1] 98
head(top_posCor, 20L)
## # A tibble: 20 × 3
##    analytes     estimate.rho   p.value
##    <chr>               <dbl>     <dbl>
##  1 seq.7655.11         0.95  0.0000876
##  2 seq.9942.2          0.95  0.0000876
##  3 seq.15326.64        0.933 0.000236 
##  4 seq.6444.15         0.933 0.000236 
##  5 seq.3362.61         0.917 0.000507 
##  6 seq.12988.49        0.9   0.000943 
##  7 seq.15640.54        0.9   0.000943 
##  8 seq.16890.37        0.9   0.000943 
##  9 seq.9266.1          0.9   0.000943 
## 10 seq.16785.45        0.883 0.00159  
## 11 seq.3336.50         0.883 0.00159  
## 12 seq.4666.199        0.883 0.00159  
## 13 seq.8304.50         0.883 0.00159  
## 14 seq.2944.66         0.867 0.00250  
## 15 seq.3434.34         0.867 0.00250  
## 16 seq.3435.53         0.867 0.00250  
## 17 seq.3440.7          0.867 0.00250  
## 18 seq.4131.72         0.867 0.00250  
## 19 seq.4907.56         0.867 0.00250  
## 20 seq.4914.10         0.867 0.00250

The table above contains analytes that have a strong positive correlation with Age, but this information alone may not enough to derive meaningful biological insights. Which proteins and genes do these identifiers correspond to? Are the most correlated proteins functionally related in some way, perhaps as part of the same biological pathway? These are the types of questions that SomaScan.db is designed to address.

In the next section, we will annotate these data by querying the above SeqIds in SomaScan.db to retrieve additional information about their corresponding genes and gene types.

4 Annotating Results

To obtain a list of available annotations, use the columns method:

columns(SomaScan.db)
##  [1] "ACCNUM"       "ALIAS"        "ENSEMBL"      "ENSEMBLPROT"  "ENSEMBLTRANS"
##  [6] "ENTREZID"     "ENZYME"       "EVIDENCE"     "EVIDENCEALL"  "GENENAME"    
## [11] "GENETYPE"     "GO"           "GOALL"        "IPI"          "MAP"         
## [16] "OMIM"         "ONTOLOGY"     "ONTOLOGYALL"  "PATH"         "PFAM"        
## [21] "PMID"         "PROBEID"      "PROSITE"      "REFSEQ"       "SYMBOL"      
## [26] "UCSCKG"       "UNIPROT"

Note that the “PROBEID” column corresponds to the SomaScan SeqId, the central probe for the platform. This identifier ties the other available annotations (listed in the columns output above) to the data found in an ADAT file. For more information on the ADAT file format and an explanation of its contents, please reference the SomaLogic-Data GitHub repository.

For this example, we will retrieve Gene Ontology (GO) identifiers associated with the SeqIds that are positively correlated with Age. This will be the first step in identifying biological processes associated with the protein targets of these SeqIds.

grep("GO|ONTOLOGY", columns(SomaScan.db), value = TRUE)
## [1] "GO"          "GOALL"       "ONTOLOGY"    "ONTOLOGYALL"

The GO and GOALL columns both contain GO pathway identifiers, while
ONTOLOGY and ONTOLOGYALL contain additional metadata about the identifiers. For additional information about the values returned by columns, run help("{COLUMN NAME}") to get a more detailed description of the listed options.


4.1 Retrieving Annotations

The select method can be used to query the annotations to retrieve information corresponding to SomaScan analytes of interest. But, before we proceed, a note about the select method.


4.1.1 select Namespace Collisions

The select method is unique to Bioconductor’s annotation packages (of which SomaScan.db is one), and should not be confused with the similarly-named dplyr::select(). These two functions perform very different actions on different classes of objects. If you have the dplyr package (dplyr) loaded at the same time as SomaScan.db (as we do in this vignette), you may encounter an error like the one below when using select:

Error in UseMethod("select") : 
  no applicable method for 'select' applied to an object of class "c('SomaDb', 
  'ChipDb', 'AnnotationDb', 'envRefClass', '.environment', 'refClass', 
  'environment', 'refObject', 'AssayData')"

This error indicates that it is unclear which select you are attempting to use (the dplyr version or the SomaScan.db version). To remedy this, it can be helpful to use the :: operator to specify the package namespace when calling select, as seen in the code chunk below.


4.1.2 Gene Name Annotation

Continuing on with the example, we will retrieve gene names (as symbols) that correspond to the top 10 analytes associated with Age.

top10_analytes <- head(top_posCor$analytes, 10L)

anno <- SomaScan.db::select(SomaScan.db, 
                            keys = top10_analytes,
                            columns = c("SYMBOL", "GENENAME", "GENETYPE"))
## 'select()' returned 1:1 mapping between keys and columns
anno
##     PROBEID   SYMBOL                                         GENENAME
## 1   7655-11     NPPB                            natriuretic peptide B
## 2    9942-2     NXT1  nuclear transport factor 2 like export factor 1
## 3  15326-64     GBP1                      guanylate binding protein 1
## 4   6444-15     PSG3         pregnancy specific beta-1-glycoprotein 3
## 5   3362-61   CHRDL1                                   chordin like 1
## 6  12988-49    EWSR1                        EWS RNA binding protein 1
## 7  15640-54    TAGLN                                       transgelin
## 8  16890-37 ADAMTSL1                                    ADAMTS like 1
## 9    9266-1    TREM1 triggering receptor expressed on myeloid cells 1
## 10 16785-45    DEFA5                                 defensin alpha 5
##          GENETYPE
## 1  protein-coding
## 2  protein-coding
## 3  protein-coding
## 4  protein-coding
## 5  protein-coding
## 6  protein-coding
## 7  protein-coding
## 8  protein-coding
## 9  protein-coding
## 10 protein-coding

Remember that select retains the order of the original query, so these genes are still listed in order of most highly associated with Age.


4.1.3 GO Annotation

Which pathways or biological processes are these genes associated with? Could that information help explain why they positively correlated with age? SomaScan.db enables mapping between SeqIds and GO identifiers, so let’s take the top 3 genes and add GO annotations to the data frame. But why only 3 genes? We are likely to receive a lot of additional information if we query the database for GO identifiers, so it can be easier and cleaner to begin with a small example data set when retrieving additional annotations.

go_anno <- SomaScan.db::select(SomaScan.db, 
                               keys = anno$PROBEID[1:3L],
                               columns = c("SYMBOL", "GENENAME", "GENETYPE", 
                                           "GO", "ONTOLOGY")) %>%
    dplyr::filter(ONTOLOGY == "BP")
## 'select()' returned 1:many mapping between keys and columns
go_anno
##     PROBEID SYMBOL                                        GENENAME
## 1   7655-11   NPPB                           natriuretic peptide B
## 2   7655-11   NPPB                           natriuretic peptide B
## 3   7655-11   NPPB                           natriuretic peptide B
## 4   7655-11   NPPB                           natriuretic peptide B
## 5   7655-11   NPPB                           natriuretic peptide B
## 6   7655-11   NPPB                           natriuretic peptide B
## 7   7655-11   NPPB                           natriuretic peptide B
## 8   7655-11   NPPB                           natriuretic peptide B
## 9   7655-11   NPPB                           natriuretic peptide B
## 10  7655-11   NPPB                           natriuretic peptide B
## 11  7655-11   NPPB                           natriuretic peptide B
## 12  7655-11   NPPB                           natriuretic peptide B
## 13  7655-11   NPPB                           natriuretic peptide B
## 14  7655-11   NPPB                           natriuretic peptide B
## 15  7655-11   NPPB                           natriuretic peptide B
## 16  7655-11   NPPB                           natriuretic peptide B
## 17  7655-11   NPPB                           natriuretic peptide B
## 18  7655-11   NPPB                           natriuretic peptide B
## 19  7655-11   NPPB                           natriuretic peptide B
## 20   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 21   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 22   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 23   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 24 15326-64   GBP1                     guanylate binding protein 1
## 25 15326-64   GBP1                     guanylate binding protein 1
## 26 15326-64   GBP1                     guanylate binding protein 1
## 27 15326-64   GBP1                     guanylate binding protein 1
## 28 15326-64   GBP1                     guanylate binding protein 1
## 29 15326-64   GBP1                     guanylate binding protein 1
## 30 15326-64   GBP1                     guanylate binding protein 1
## 31 15326-64   GBP1                     guanylate binding protein 1
## 32 15326-64   GBP1                     guanylate binding protein 1
## 33 15326-64   GBP1                     guanylate binding protein 1
## 34 15326-64   GBP1                     guanylate binding protein 1
## 35 15326-64   GBP1                     guanylate binding protein 1
## 36 15326-64   GBP1                     guanylate binding protein 1
## 37 15326-64   GBP1                     guanylate binding protein 1
## 38 15326-64   GBP1                     guanylate binding protein 1
## 39 15326-64   GBP1                     guanylate binding protein 1
## 40 15326-64   GBP1                     guanylate binding protein 1
## 41 15326-64   GBP1                     guanylate binding protein 1
## 42 15326-64   GBP1                     guanylate binding protein 1
##          GENETYPE         GO EVIDENCE ONTOLOGY
## 1  protein-coding GO:0003085      IBA       BP
## 2  protein-coding GO:0003161      NAS       BP
## 3  protein-coding GO:0006182      IBA       BP
## 4  protein-coding GO:0006182      IDA       BP
## 5  protein-coding GO:0006457      IDA       BP
## 6  protein-coding GO:0007166      NAS       BP
## 7  protein-coding GO:0007168      IBA       BP
## 8  protein-coding GO:0007168      IDA       BP
## 9  protein-coding GO:0007218      IBA       BP
## 10 protein-coding GO:0007589      TAS       BP
## 11 protein-coding GO:0008217      NAS       BP
## 12 protein-coding GO:0016525      TAS       BP
## 13 protein-coding GO:0019934      IBA       BP
## 14 protein-coding GO:0030308      NAS       BP
## 15 protein-coding GO:0035810      TAS       BP
## 16 protein-coding GO:0035815      TAS       BP
## 17 protein-coding GO:0042311      IEA       BP
## 18 protein-coding GO:0043114      TAS       BP
## 19 protein-coding GO:0097746      NAS       BP
## 20 protein-coding GO:0006406      IDA       BP
## 21 protein-coding GO:0006406      ISS       BP
## 22 protein-coding GO:0006611      IEA       BP
## 23 protein-coding GO:0016973      IBA       BP
## 24 protein-coding GO:0032703      IMP       BP
## 25 protein-coding GO:0042742      ISS       BP
## 26 protein-coding GO:0042832      IDA       BP
## 27 protein-coding GO:0045087      IDA       BP
## 28 protein-coding GO:0050848      IMP       BP
## 29 protein-coding GO:0050860      IMP       BP
## 30 protein-coding GO:0051607      IEA       BP
## 31 protein-coding GO:0051715      IDA       BP
## 32 protein-coding GO:0070373      IMP       BP
## 33 protein-coding GO:0071346      IBA       BP
## 34 protein-coding GO:0071346      IDA       BP
## 35 protein-coding GO:0071347      IEP       BP
## 36 protein-coding GO:0071356      IEP       BP
## 37 protein-coding GO:0072665      IDA       BP
## 38 protein-coding GO:0140639      IDA       BP
## 39 protein-coding GO:0160075      IDA       BP
## 40 protein-coding GO:1900025      IMP       BP
## 41 protein-coding GO:1903076      IGI       BP
## 42 protein-coding GO:1903077      IMP       BP

As expected when working with GO terms, there were quite a few rows retrieved by that select query (42 rows of information for only 3 genes). Filtering the results to the biological process (“BP”) ontology only can help reduce the number of GO identifiers that are returned in the query.

This leaves us with a list of GO identifiers, but those identifiers do not adequately explain much about the term itself. How can we get more “human-readable” information out of GO?

Luckily, this is easy to do with other annotation tools from Bioconductor. The GO.db annotation package contains annotations describing the
entire Gene Ontology knowledgebase, assembled using data directly from the GO website. We can use the GO IDs identified by SomaScan.db to connect with GO.db and retrieve more information about each GO ID.

go_terms <- AnnotationDbi::select(GO.db, 
                                  keys = go_anno$GO, 
                                  columns = c("GOID", "TERM", "DEFINITION"))
## 'select()' returned many:1 mapping between keys and columns
go_terms
##          GOID
## 1  GO:0003085
## 2  GO:0003161
## 3  GO:0006182
## 4  GO:0006182
## 5  GO:0006457
## 6  GO:0007166
## 7  GO:0007168
## 8  GO:0007168
## 9  GO:0007218
## 10 GO:0007589
## 11 GO:0008217
## 12 GO:0016525
## 13 GO:0019934
## 14 GO:0030308
## 15 GO:0035810
## 16 GO:0035815
## 17 GO:0042311
## 18 GO:0043114
## 19 GO:0097746
## 20 GO:0006406
## 21 GO:0006406
## 22 GO:0006611
## 23 GO:0016973
## 24 GO:0032703
## 25 GO:0042742
## 26 GO:0042832
## 27 GO:0045087
## 28 GO:0050848
## 29 GO:0050860
## 30 GO:0051607
## 31 GO:0051715
## 32 GO:0070373
## 33 GO:0071346
## 34 GO:0071346
## 35 GO:0071347
## 36 GO:0071356
## 37 GO:0072665
## 38 GO:0140639
## 39 GO:0160075
## 40 GO:1900025
## 41 GO:1903076
## 42 GO:1903077
##                                                                  TERM
## 1             negative regulation of systemic arterial blood pressure
## 2                               cardiac conduction system development
## 3                                           cGMP biosynthetic process
## 4                                           cGMP biosynthetic process
## 5                                                     protein folding
## 6                             cell surface receptor signaling pathway
## 7                         receptor guanylyl cyclase signaling pathway
## 8                         receptor guanylyl cyclase signaling pathway
## 9                                      neuropeptide signaling pathway
## 10                                               body fluid secretion
## 11                                       regulation of blood pressure
## 12                                negative regulation of angiogenesis
## 13                                            cGMP-mediated signaling
## 14                                 negative regulation of cell growth
## 15                                positive regulation of urine volume
## 16                      positive regulation of renal sodium excretion
## 17                                                       vasodilation
## 18                                regulation of vascular permeability
## 19                                  blood vessel diameter maintenance
## 20                                           mRNA export from nucleus
## 21                                           mRNA export from nucleus
## 22                                        protein export from nucleus
## 23                                  poly(A)+ mRNA export from nucleus
## 24                    negative regulation of interleukin-2 production
## 25                                      defense response to bacterium
## 26                                      defense response to protozoan
## 27                                             innate immune response
## 28                           regulation of calcium-mediated signaling
## 29           negative regulation of T cell receptor signaling pathway
## 30                                          defense response to virus
## 31                                      cytolysis in another organism
## 32                       negative regulation of ERK1 and ERK2 cascade
## 33                            cellular response to type II interferon
## 34                            cellular response to type II interferon
## 35                                 cellular response to interleukin-1
## 36                         cellular response to tumor necrosis factor
## 37                                    protein localization to vacuole
## 38                                  positive regulation of pyroptosis
## 39                        non-canonical inflammasome complex assembly
## 40 negative regulation of substrate adhesion-dependent cell spreading
## 41              regulation of protein localization to plasma membrane
## 42     negative regulation of protein localization to plasma membrane
##                                                                                                                                                                                                                                                                                                                                                                                                          DEFINITION
## 1                                                                                                                                                                                                                                                                                                     The process that reduces the force with which blood travels through the systemic arterial circulatory system.
## 2                                                                                                                                                     The process whose specific outcome is the progression of the cardiac conduction system over time, from its formation to the mature structure. The cardiac conduction system consists of specialized cardiomyocytes that regulate the frequency of heart beat.
## 3                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 4                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 5                                                                                                                                                                                                                                                     The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure.
## 6  The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
## 7                                                                                                                                         The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 8                                                                                                                                         The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 9                                                                                                                                                                                                              A G protein-coupled receptor signaling pathway initiated by a neuropeptide binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process.
## 10                                                                                                                                                                                                                                                                                                                                              The controlled release of a fluid by a cell or tissue in an animal.
## 11                                                                                                                                                                                                                  Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure.
## 12                                                                                                                                                                                                                                                                                                                      Any process that stops, prevents, or reduces the frequency, rate or extent of angiogenesis.
## 13                                                                                                                                                                                                                         An intracellular signaling cassette that starts with production of cyclic GMP (cGMP), and ends with activation of downstream effectors that further transmit the signal within the cell.
## 14                                                                                                                                                                                                                                                                                                            Any process that stops, prevents, or reduces the frequency, rate, extent or direction of cell growth.
## 15                                                                                                                                                                                                                                                                                                                       Any process that increases the amount of urine excreted from the body over a unit of time.
## 16                                                                                                                                                                                                                                                                                                                           Any process that increases the amount of sodium excreted in urine over a unit of time.
## 17                                                                                                                                                                                              An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure.
## 18                                                                                                                                                                                                                                                                                                                           Any process that modulates the extent to which blood vessels can be pervaded by fluid.
## 19                                                                                                                                                                                                                                                                                                                                                        Any process that modulates the diameter of blood vessels.
## 20                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 21                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 22                                                                                                                                                                                                                                                                                                                                          The directed movement of a protein from the nucleus into the cytoplasm.
## 23                                                                                                                                                                                                                                                                                                                                    The directed movement of poly(A)+ mRNA out of the nucleus into the cytoplasm.
## 24                                                                                                                                                                                                                                                                                                         Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-2 production.
## 25                                                                                                                                                                                                                                                                                                         Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism.
## 26                                                                                                                                                                                                                                                                                                         Reactions triggered in response to the presence of a protozoan that act to protect the cell or organism.
## 27                                                                                                                                                                                                                                                                 Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
## 28                                                                                                                                                                                                                        Any process that modulates the frequency, rate or extent of calcium-mediated signaling, the process in which a cell uses calcium ions to convert an extracellular signal into a response.
## 29                                                                                                                                                                                                                                              Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell.
## 30                                                                                                                                                                                                                                                                                                             Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
## 31                                                                                                                                                                                                                                                                                    The killing by an organism of a cell in another organism by means of the rupture of cell membranes and the loss of cytoplasm.
## 32                                                                                                                                                                                                                                                                         Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
## 33                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 34                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 35                                                                                                                                                                                                                        Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
## 36                                                                                                                                                                                                                 Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
## 37                                                                                                                                                                                                                                                                                                                       A process in which a protein is transported to, or maintained at, a location in a vacuole.
## 38                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 39                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 40                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 41                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 42                                                                                                                                                                                                                                                                                                                                                                                                             <NA>

Now we have much more information about each GO ID! Using these IDs, we can merge this information back into our select results from SomaScan.db:

final_df <- left_join(go_anno, go_terms, by = c("GO" = "GOID"))
## Warning in left_join(go_anno, go_terms, by = c(GO = "GOID")): Detected an unexpected many-to-many relationship between `x` and `y`.
## ℹ Row 3 of `x` matches multiple rows in `y`.
## ℹ Row 3 of `y` matches multiple rows in `x`.
## ℹ If a many-to-many relationship is expected, set `relationship =
##   "many-to-many"` to silence this warning.
final_df
##     PROBEID SYMBOL                                        GENENAME
## 1   7655-11   NPPB                           natriuretic peptide B
## 2   7655-11   NPPB                           natriuretic peptide B
## 3   7655-11   NPPB                           natriuretic peptide B
## 4   7655-11   NPPB                           natriuretic peptide B
## 5   7655-11   NPPB                           natriuretic peptide B
## 6   7655-11   NPPB                           natriuretic peptide B
## 7   7655-11   NPPB                           natriuretic peptide B
## 8   7655-11   NPPB                           natriuretic peptide B
## 9   7655-11   NPPB                           natriuretic peptide B
## 10  7655-11   NPPB                           natriuretic peptide B
## 11  7655-11   NPPB                           natriuretic peptide B
## 12  7655-11   NPPB                           natriuretic peptide B
## 13  7655-11   NPPB                           natriuretic peptide B
## 14  7655-11   NPPB                           natriuretic peptide B
## 15  7655-11   NPPB                           natriuretic peptide B
## 16  7655-11   NPPB                           natriuretic peptide B
## 17  7655-11   NPPB                           natriuretic peptide B
## 18  7655-11   NPPB                           natriuretic peptide B
## 19  7655-11   NPPB                           natriuretic peptide B
## 20  7655-11   NPPB                           natriuretic peptide B
## 21  7655-11   NPPB                           natriuretic peptide B
## 22  7655-11   NPPB                           natriuretic peptide B
## 23  7655-11   NPPB                           natriuretic peptide B
## 24   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 25   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 26   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 27   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 28   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 29   9942-2   NXT1 nuclear transport factor 2 like export factor 1
## 30 15326-64   GBP1                     guanylate binding protein 1
## 31 15326-64   GBP1                     guanylate binding protein 1
## 32 15326-64   GBP1                     guanylate binding protein 1
## 33 15326-64   GBP1                     guanylate binding protein 1
## 34 15326-64   GBP1                     guanylate binding protein 1
## 35 15326-64   GBP1                     guanylate binding protein 1
## 36 15326-64   GBP1                     guanylate binding protein 1
## 37 15326-64   GBP1                     guanylate binding protein 1
## 38 15326-64   GBP1                     guanylate binding protein 1
## 39 15326-64   GBP1                     guanylate binding protein 1
## 40 15326-64   GBP1                     guanylate binding protein 1
## 41 15326-64   GBP1                     guanylate binding protein 1
## 42 15326-64   GBP1                     guanylate binding protein 1
## 43 15326-64   GBP1                     guanylate binding protein 1
## 44 15326-64   GBP1                     guanylate binding protein 1
## 45 15326-64   GBP1                     guanylate binding protein 1
## 46 15326-64   GBP1                     guanylate binding protein 1
## 47 15326-64   GBP1                     guanylate binding protein 1
## 48 15326-64   GBP1                     guanylate binding protein 1
## 49 15326-64   GBP1                     guanylate binding protein 1
## 50 15326-64   GBP1                     guanylate binding protein 1
##          GENETYPE         GO EVIDENCE ONTOLOGY
## 1  protein-coding GO:0003085      IBA       BP
## 2  protein-coding GO:0003161      NAS       BP
## 3  protein-coding GO:0006182      IBA       BP
## 4  protein-coding GO:0006182      IBA       BP
## 5  protein-coding GO:0006182      IDA       BP
## 6  protein-coding GO:0006182      IDA       BP
## 7  protein-coding GO:0006457      IDA       BP
## 8  protein-coding GO:0007166      NAS       BP
## 9  protein-coding GO:0007168      IBA       BP
## 10 protein-coding GO:0007168      IBA       BP
## 11 protein-coding GO:0007168      IDA       BP
## 12 protein-coding GO:0007168      IDA       BP
## 13 protein-coding GO:0007218      IBA       BP
## 14 protein-coding GO:0007589      TAS       BP
## 15 protein-coding GO:0008217      NAS       BP
## 16 protein-coding GO:0016525      TAS       BP
## 17 protein-coding GO:0019934      IBA       BP
## 18 protein-coding GO:0030308      NAS       BP
## 19 protein-coding GO:0035810      TAS       BP
## 20 protein-coding GO:0035815      TAS       BP
## 21 protein-coding GO:0042311      IEA       BP
## 22 protein-coding GO:0043114      TAS       BP
## 23 protein-coding GO:0097746      NAS       BP
## 24 protein-coding GO:0006406      IDA       BP
## 25 protein-coding GO:0006406      IDA       BP
## 26 protein-coding GO:0006406      ISS       BP
## 27 protein-coding GO:0006406      ISS       BP
## 28 protein-coding GO:0006611      IEA       BP
## 29 protein-coding GO:0016973      IBA       BP
## 30 protein-coding GO:0032703      IMP       BP
## 31 protein-coding GO:0042742      ISS       BP
## 32 protein-coding GO:0042832      IDA       BP
## 33 protein-coding GO:0045087      IDA       BP
## 34 protein-coding GO:0050848      IMP       BP
## 35 protein-coding GO:0050860      IMP       BP
## 36 protein-coding GO:0051607      IEA       BP
## 37 protein-coding GO:0051715      IDA       BP
## 38 protein-coding GO:0070373      IMP       BP
## 39 protein-coding GO:0071346      IBA       BP
## 40 protein-coding GO:0071346      IBA       BP
## 41 protein-coding GO:0071346      IDA       BP
## 42 protein-coding GO:0071346      IDA       BP
## 43 protein-coding GO:0071347      IEP       BP
## 44 protein-coding GO:0071356      IEP       BP
## 45 protein-coding GO:0072665      IDA       BP
## 46 protein-coding GO:0140639      IDA       BP
## 47 protein-coding GO:0160075      IDA       BP
## 48 protein-coding GO:1900025      IMP       BP
## 49 protein-coding GO:1903076      IGI       BP
## 50 protein-coding GO:1903077      IMP       BP
##                                                                  TERM
## 1             negative regulation of systemic arterial blood pressure
## 2                               cardiac conduction system development
## 3                                           cGMP biosynthetic process
## 4                                           cGMP biosynthetic process
## 5                                           cGMP biosynthetic process
## 6                                           cGMP biosynthetic process
## 7                                                     protein folding
## 8                             cell surface receptor signaling pathway
## 9                         receptor guanylyl cyclase signaling pathway
## 10                        receptor guanylyl cyclase signaling pathway
## 11                        receptor guanylyl cyclase signaling pathway
## 12                        receptor guanylyl cyclase signaling pathway
## 13                                     neuropeptide signaling pathway
## 14                                               body fluid secretion
## 15                                       regulation of blood pressure
## 16                                negative regulation of angiogenesis
## 17                                            cGMP-mediated signaling
## 18                                 negative regulation of cell growth
## 19                                positive regulation of urine volume
## 20                      positive regulation of renal sodium excretion
## 21                                                       vasodilation
## 22                                regulation of vascular permeability
## 23                                  blood vessel diameter maintenance
## 24                                           mRNA export from nucleus
## 25                                           mRNA export from nucleus
## 26                                           mRNA export from nucleus
## 27                                           mRNA export from nucleus
## 28                                        protein export from nucleus
## 29                                  poly(A)+ mRNA export from nucleus
## 30                    negative regulation of interleukin-2 production
## 31                                      defense response to bacterium
## 32                                      defense response to protozoan
## 33                                             innate immune response
## 34                           regulation of calcium-mediated signaling
## 35           negative regulation of T cell receptor signaling pathway
## 36                                          defense response to virus
## 37                                      cytolysis in another organism
## 38                       negative regulation of ERK1 and ERK2 cascade
## 39                            cellular response to type II interferon
## 40                            cellular response to type II interferon
## 41                            cellular response to type II interferon
## 42                            cellular response to type II interferon
## 43                                 cellular response to interleukin-1
## 44                         cellular response to tumor necrosis factor
## 45                                    protein localization to vacuole
## 46                                  positive regulation of pyroptosis
## 47                        non-canonical inflammasome complex assembly
## 48 negative regulation of substrate adhesion-dependent cell spreading
## 49              regulation of protein localization to plasma membrane
## 50     negative regulation of protein localization to plasma membrane
##                                                                                                                                                                                                                                                                                                                                                                                                          DEFINITION
## 1                                                                                                                                                                                                                                                                                                     The process that reduces the force with which blood travels through the systemic arterial circulatory system.
## 2                                                                                                                                                     The process whose specific outcome is the progression of the cardiac conduction system over time, from its formation to the mature structure. The cardiac conduction system consists of specialized cardiomyocytes that regulate the frequency of heart beat.
## 3                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 4                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 5                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 6                                                                                                                                                                                                                                                                                                          The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate.
## 7                                                                                                                                                                                                                                                     The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure.
## 8  The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
## 9                                                                                                                                         The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 10                                                                                                                                        The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 11                                                                                                                                        The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 12                                                                                                                                        The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
## 13                                                                                                                                                                                                             A G protein-coupled receptor signaling pathway initiated by a neuropeptide binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process.
## 14                                                                                                                                                                                                                                                                                                                                              The controlled release of a fluid by a cell or tissue in an animal.
## 15                                                                                                                                                                                                                  Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure.
## 16                                                                                                                                                                                                                                                                                                                      Any process that stops, prevents, or reduces the frequency, rate or extent of angiogenesis.
## 17                                                                                                                                                                                                                         An intracellular signaling cassette that starts with production of cyclic GMP (cGMP), and ends with activation of downstream effectors that further transmit the signal within the cell.
## 18                                                                                                                                                                                                                                                                                                            Any process that stops, prevents, or reduces the frequency, rate, extent or direction of cell growth.
## 19                                                                                                                                                                                                                                                                                                                       Any process that increases the amount of urine excreted from the body over a unit of time.
## 20                                                                                                                                                                                                                                                                                                                           Any process that increases the amount of sodium excreted in urine over a unit of time.
## 21                                                                                                                                                                                              An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure.
## 22                                                                                                                                                                                                                                                                                                                           Any process that modulates the extent to which blood vessels can be pervaded by fluid.
## 23                                                                                                                                                                                                                                                                                                                                                        Any process that modulates the diameter of blood vessels.
## 24                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 25                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 26                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 27                                                                                                                                                                                                                                                                                                                                                 The directed movement of mRNA from the nucleus to the cytoplasm.
## 28                                                                                                                                                                                                                                                                                                                                          The directed movement of a protein from the nucleus into the cytoplasm.
## 29                                                                                                                                                                                                                                                                                                                                    The directed movement of poly(A)+ mRNA out of the nucleus into the cytoplasm.
## 30                                                                                                                                                                                                                                                                                                         Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-2 production.
## 31                                                                                                                                                                                                                                                                                                         Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism.
## 32                                                                                                                                                                                                                                                                                                         Reactions triggered in response to the presence of a protozoan that act to protect the cell or organism.
## 33                                                                                                                                                                                                                                                                 Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
## 34                                                                                                                                                                                                                        Any process that modulates the frequency, rate or extent of calcium-mediated signaling, the process in which a cell uses calcium ions to convert an extracellular signal into a response.
## 35                                                                                                                                                                                                                                              Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell.
## 36                                                                                                                                                                                                                                                                                                             Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
## 37                                                                                                                                                                                                                                                                                    The killing by an organism of a cell in another organism by means of the rupture of cell membranes and the loss of cytoplasm.
## 38                                                                                                                                                                                                                                                                         Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
## 39                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 40                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 41                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 42                                                                                                                                         Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far.
## 43                                                                                                                                                                                                                        Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
## 44                                                                                                                                                                                                                 Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
## 45                                                                                                                                                                                                                                                                                                                       A process in which a protein is transported to, or maintained at, a location in a vacuole.
## 46                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 47                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 48                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 49                                                                                                                                                                                                                                                                                                                                                                                                             <NA>
## 50                                                                                                                                                                                                                                                                                                                                                                                                             <NA>

The SomaScan.db package can be used to link to numerous other annotation resources. For a more detailed description of how this can be done with examples of what resources are available, see the Advanced Usage Examples vignette.

There is still room for further exploration and extension of these results; this workflow is meant to be an introduction to how SomaScan.db can be used to build upon and interpret information obtained from a SomaLogic ADAT.

5 Session Info

sessionInfo()
## R version 4.4.0 beta (2024-04-15 r86425)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 22.04.4 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.19-bioc/R/lib/libRblas.so 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_GB              LC_COLLATE=C              
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: America/New_York
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats4    stats     graphics  grDevices utils     datasets  methods  
## [8] base     
## 
## other attached packages:
##  [1] SomaDataIO_6.1.0     dplyr_1.1.4          org.Hs.eg.db_3.19.1 
##  [4] KEGGREST_1.43.0      GO.db_3.19.1         tibble_3.2.1        
##  [7] SomaScan.db_0.99.10  AnnotationDbi_1.65.2 IRanges_2.37.1      
## [10] S4Vectors_0.41.7     Biobase_2.63.1       BiocGenerics_0.49.1 
## [13] withr_3.0.0          BiocStyle_2.31.0    
## 
## loaded via a namespace (and not attached):
##  [1] tidyr_1.3.1             generics_0.1.3          sass_0.4.9             
##  [4] utf8_1.2.4              RSQLite_2.3.6           digest_0.6.35          
##  [7] magrittr_2.0.3          evaluate_0.23           bookdown_0.39          
## [10] fastmap_1.1.1           blob_1.2.4              cellranger_1.1.0       
## [13] jsonlite_1.8.8          GenomeInfoDb_1.39.14    DBI_1.2.2              
## [16] BiocManager_1.30.22     httr_1.4.7              purrr_1.0.2            
## [19] fansi_1.0.6             UCSC.utils_0.99.7       Biostrings_2.71.6      
## [22] jquerylib_0.1.4         cli_3.6.2               rlang_1.1.3            
## [25] crayon_1.5.2            XVector_0.43.1          bit64_4.0.5            
## [28] cachem_1.0.8            yaml_2.3.8              tools_4.4.0            
## [31] memoise_2.0.1           GenomeInfoDbData_1.2.12 curl_5.2.1             
## [34] vctrs_0.6.5             R6_2.5.1                png_0.1-8              
## [37] lifecycle_1.0.4         zlibbioc_1.49.3         bit_4.0.5              
## [40] pkgconfig_2.0.3         bslib_0.7.0             pillar_1.9.0           
## [43] glue_1.7.0              highr_0.10              tidyselect_1.2.1       
## [46] xfun_0.43               knitr_1.46              htmltools_0.5.8.1      
## [49] rmarkdown_2.26          compiler_4.4.0          readxl_1.4.3