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INTRODUCTION: Although several programs are designed to identify variants with low allelic-fraction, further improvement is needed, especially to push the detection limit of low allelic-faction variants in low-quality, "noisy" tumor samples.

RESULTS: We developed LoLoPicker, an efficient tool dedicated to calling somatic variants from next-generation sequencing (NGS) data of tumor sample against the matched normal sample plus a user-defined control panel of additional normal samples. The control panel allows accurately estimating background error rate and therefore ensures high-accuracy mutation detection.

CONCLUSIONS: Compared to other methods, we showed a superior performance of LoLoPicker with significantly improved specificity. The algorithm of LoLoPicker is particularly useful for calling low allelic-fraction variants from low-quality cancer samples such as formalin-fixed and paraffin-embedded (FFPE) samples.Implementation and Availability: The main scripts are implemented in Python-2.7 and the package is released at .