PureCLIP 1.3.1

• Fixed bug concerning initialisation of data with extreme outliers, caused error due to emission probabilities of 0.

PureCLIP 1.3.0

• Extension to handle individual replicates (currently only two). Emission probability parameters are learned for each replicate separately. Joint emission probabilities are then used in the final HMM.

• Added user option '-st' to choose alternative crosslink site scoring scheme, which is also used to compute scores for binding regions. For the called crosslink sites alternative scores are reported in column 7.

• GLM to learn correlation between input control and target signals: added check and re-seeding to ensure that the expected value for the 'enriched' state remains greater than the expected value for the 'non-enriched' state across range of input fragment density values.

PureCLIP 1.2.0

• Forward-Backward algorithm: changed from scaling method to computation in log-space using log-sum-exp trick. Runtime not significantly affected due to precomputations. Increased numerical stability (parameter -ld should not be needed anymore).

• Fixed bug when applying HMM only to subset using parameter '-chr' (introduced in last version).

• Minor fix in script for computing CL-motif scores: allow contig names containing "_"

PureCLIP 1.1.2

• No longer writes temporary BED files
• Automatically set number of threads used for application of learned model (-nta) depended on other parameters, if not provided by user
• Fixed check for correct ordering of gamma distributions

PureCLIP 1.1.1

• Minor fix in processing of covered intervals.

• Added pseudo emission probabilities for borders of binomial distributions for very large values. Allows sites to be called as crosslink sites, even if emission probabilities becoming 0.0 and prevents interval from being discarded.

• Increased limits of max. stored read start values and estimated n values.

• Increased default value of max. read start count within interval to allow interval be used for learning to 500.

PureCLIP 1.1.0

• Fixed bug in HMM application part concerning the elimination of intervals containing emission probabilities of 0.0. Whole interval is discarded now.

• Fixed floating point error in normalisation of left-truncated gamma distribution.

• Minor fix regarding content and filename of model parameter output. User parameter '-p' is applied now, or '.params' is appended to base of crosslink site output filename.

• Changed floating point precision for various intermediate computations.

• Added error handling regarding emission probabilities getting close precision limits.

• Changed initialisation of gamma distributions. Nelder-Mead simplex algorithm is applied directly to multidimensional problem and restarted for different start values. For the gamma GLM initialisation first parameters are estimated for the compound gamma distribution. Based on these start values are chosen for the 'non-enriched' and 'enriched' simplex procedure and state posterior probabilities are assigned based on the expected value.

• Changed handling of parameter constraints in combination with the simplex algorithm. Instead of fixing gamma shape parameter values when the algorithm is running out of constraints, the likelihood landscape outside of the constraints and seen by the GSL simplex algorithm is modified and penalties depending on the distance are applied. Gamma mean values are estimated in log-space.

PureCLIP 1.0.5

• Updated compute_CLmotif_scores script to handle newer versions of meme (up to 5.0.1)

• Fixed bug regarding end position of merged binding regions (forward strand)

• Added user option to define crosslink positions relative to read starts

• Added user option to select R1 or R2 for analysis

• Minor changes in error handling

PureCLIP 1.0.4

• decoupled bandwidth to access enrichment from bandwidth used to estimate binomial n parameter

• added option to apply n threshold for learning of transition probabilities '2' -> '2'/'3'

• added user option to enable automatic computation of suitable n threshold

• Fixed initial estimation of transition probabilities

• added user option with flag for proteins with different binding characteristics

PureCLIP 1.0.3

• Fixed bug regarding contigNames in FASTA files not present in BAM file
• Added user option for high precision emission probability computation (useful in case of extreme outliers, e.g. extreme high read start counts with emission probabilities close to zero)

PureCLIP 1.0.2

• Fixed bug within estimation of n_t
• Added option to allow unconstrained gamma shapes for GLM version
• Removed limitation regarding position-wise read start counts for application of HMM