As directed in the Monocle 2 Documentation, the cellDataSet constructor is called on a sparse matrix and two AnnotatedDataFrames. Here is the suggested usage:

pd <- new("AnnotatedDataFrame", data = sample_sheet)
fd <- new("AnnotatedDataFrame", data = gene_annotation)
cds <- newCellDataSet(expr_matrix, phenoData = pd, featureData = fd)

Below, I show the matrix I am working with and the two AnnotatedDataFrames. When I attempt to create the new CellDataSet, I get an error that refers to the assayData parameter of CellDataSet's parent class, ExpressionSet. However, as far as I can tell, the assayData parameter (which is of type AnnotatedDataFrame) is replaced by a sparse matrix in Monocle 2's CellDataSet, so this error is cryptic.

> head(combined_mat_trimmed)
6 x 904 sparse Matrix of class "dgCMatrix"
   [[ suppressing 51 column names ‘Edge1_AAACGGGGTACCGTTA’, ‘Edge1_AAACGGGTCTGGCGAC’, ‘Edge1_AAAGATGAGCCTCGTG’ ... ]]

RP11-791M20.1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ARIH2OS       . 2 . . . . . . . . 1 . . . . 1 . . . . . 1 1 1 . . . . . . . . . 1 . . . . 1 . . . . . 1 . . . . .
RP11-5P4.3    . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RP11-561E1.1  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PROSC         1 . . . . 1 1 . . 1 . 1 . 1 . 4 2 1 . 2 1 . 1 2 . . 2 . 2 1 3 . . 5 . . 3 . 1 2 1 1 3 3 1 1 . 4 . 3
RP11-744I24.3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

RP11-791M20.1 . ......
ARIH2OS       . ......
RP11-5P4.3    . ......
RP11-561E1.1  . ......
PROSC         1 ......
RP11-744I24.3 . ......

 .....suppressing columns in show(); maybe adjust 'options(max.print= *, width = *)'
 ..............................
> head(fd)
An object of class 'AnnotatedDataFrame'
  rowNames: RP11-34P13.7 FO538757.2 ... RP11-206L10.9 (6 total)
  varLabels: System
  varMetadata: labelDescription
> head(pd)
An object of class 'AnnotatedDataFrame'
  rowNames: Edge1_AAACGGGGTACCGTTA Edge1_AAACGGGTCTGGCGAC ... Edge1_AAAGTAGCAGCTCGAC (6 total)
  varLabels: Replicate
  varMetadata: labelDescription
> colonTumor <- newCellDataSet(combined_mat_trimmed, phenoData=pd, featureData=fd)
Error in validObject(.Object) : 
  invalid class “CellDataSet” object: featureNames differ between assayData and featureData
In addition: Warning messages:
1: In newCellDataSet(combined_mat_trimmed, phenoData = pd, featureData = fd) :
  Warning: featureData must contain a column verbatim named 'gene_short_name' for certain functions
2: In newCellDataSet(combined_mat_trimmed, phenoData = pd, featureData = fd) :
  Warning: featureData must contain a column verbatim named 'gene_short_name' for certain functions
3: In newCellDataSet(combined_mat_trimmed, phenoData = pd, featureData = fd) :
  Warning: featureData must contain a column verbatim named 'gene_short_name' for certain functions