. B: Bioinformatic analyses of peptide sequences (Specific aim 1) I) Sequencing of peptides: Sequence reads are obtained from phage DNA libraries generated and analyzed with high-throughput sequencing (Illumina HiSeq system). Quality control checks are performed using FastQC tool. The reads are processed to trim adaptors and remove the consensus sequences from either side using the Cutadapt software (23). The remaining fragment tags contain the peptides' DNA sequence and are expected to be 21 nucleotides in length. Next, the BioString package from the Bioconductor framework are used to translate these nucleotide sequences, and the number of occurrences of each peptide sequence is calculated to find the most frequent peptides. Following normalization to library size, peptide sequence counts from different patient libraries are compared to find common sequences. Sequences from the membrane-bound pool fraction are subtracted from the internalized pool fraction so as to remove membrane-bound clones that may not have been successfully eluted off the CLL cell. The sequences remaining in the internalized pool serve as candidates for peptide-conjugate therapy. A univariate logistic regression approach will then be used to test possible associations of peptide counts with clinical and genetic findings. When clinical parameters are treated as continuous variables, linear regression will be implemented. Candidate peptides will be queried against the PepBank database (24) in order to check if they are known to be related to cancer or other diseases and conditions such as apoptosis or angiogenesis. Finally, a bioinformatic pipeline script will be developed automating the above bioinformatics analysis steps.