For the TCGA COAD HTSeq count data matrix from UCSC Xena, what is the best way to input it into DESeq2 to do DE analysis at gene level? The data matrix is 60488x513, which seems to be not at gene level. Right now, DESeq2 vignette only shows an example to handle HTseq count data files under a folder. Thanks!

It is not gene level counts?

If it is gene level counts, use DESeqDataSetFromMatrix.