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CoPRO analysis scripts

Scripts to facilitate analysis of CoPRO datasets.

Change Log:

v1.0: Initial commit of Preprocessing and Mappability files. There are slight differences from the analysis reported in Nature Genetics:

  • R2 barcode trimming was conditioned on the R1 barcode to minimize mismatched R1/R2 trims.
  • Insert size bias normalization uses recently reported measurements for the NextSeq (https://www.biorxiv.org/content/early/2018/08/09/388108.1).
  • These changes do not significantly affect any conclusions reported in the manuscript.

Terminology

TSN = Transcription start nucleotide TSS = Transcription start site (clusters of TSNs) TID = Transcription initiation domain (clusters of TSSes) maxTSN = Max start nucleotide within a TSS maxTSS = Max start site within a TID MMRL = Minimum mappable RNA length for a TSN (useful for avoiding mapping biases)

Preprocessing

  1. Trim barcodes & perform sequence alignment (CoPRO_align.sh)
  2. Pool multiple sequencing lanes (samtools merge)
  3. Read, filter, and adjust alignments (ConvertBams.r)
  4. Normalize & create an integrated dataset (MergeTreatments.r)
  5. Global analysis to identify TSNs, TSSes, and TIDs (CoPRO_IdentifyAll.ipynb)

Mappability lengths

  1. Extract all TSN sequences as 19-24mers (Mapping_ExtractSeqs.r)
  2. Align extracted sequences (Mapping_AlignSeqs.sh)
  3. Record MMRL for each TSN (Mapping_RecordMMRL.r)

Initiation, capping & pausing analyses

  • TSN_PauseSharing.ipynb: analysis of pause sites shared by TSNs
  • maxTSN_Pausing.ipynb: pause classification and analysis at maxTSNs
  • maxTSN_PauseReplicates.r: comparison of maxTSN pausing in each replicate
  • maxTSN_JointProbAnalysis.r: comparison of pause distributions using joint probabilities
  • maxTSN_Capping.ipynb: capping analysis at maxTSNs
  • maxTSN_SeqHeatmaps.r: analysis of GC content vs pause distance at maxTSNs
  • maxTSN_PauseClassMotifs.r: analysis of TF motifs around maxTSNs
  • maxTSN_Spacing.r: analysis of spacing between all maxTSNs (convergent, divergent, same-strand)

Transcription initiation domains

  • TID_LinearHeatmaps.ipynb: Generate linear averaged (and raw) heatmaps of ChIP datasets around TIDs

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Analysis tools for CoPRO data sets

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