EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data

Epigenetics has become a fundamental
scientific discipline with
various implications for biology and medicine. Epigenetic marks, mostly
DNA methylation and histone post-translational modifications (PTMs),
play important roles in chromatin structure and function. Accurate
quantification of these marks is an ongoing challenge due to the variety
of modifications and their wide dynamic range of abundance. Here we
present EpiProfile 2.0, an extended version of our 2015 software (v1.0),
for accurate quantification of histone peptides based on liquid chromatography–tandem
mass spectrometry (LC–MS/MS) analysis. EpiProfile 2.0 is now
optimized for data-independent acquisition through the use of precursor
and fragment extracted ion chromatography to accurately determine
the chromatographic profile and to discriminate isobaric forms of
peptides. The software uses an intelligent retention time prediction
trained on the analyzed samples to enable accurate peak detection.
EpiProfile 2.0 supports label-free and isotopic labeling, different
organisms, known sequence mutations in diseases, different derivatization
strategies, and unusual PTMs (such as acyl-derived modifications).
In summary, EpiProfile 2.0 is a universal and accurate platform for
the quantification of histone marks via LC–MS/MS. Being the
first software of its kind, we anticipate that EpiProfile 2.0 will
play a fundamental role in epigenetic studies relevant to biology
and translational medicine. EpiProfile is freely available at https://github.com/zfyuan/EpiProfile2.0_Family.

表观遗传学（Epigenetics）现已成为一门基础科学学科，对生物学与医学领域具有多方面的深远影响。表观遗传标记（epigenetic marks）主要包括DNA甲基化与组蛋白翻译后修饰（post-translational modifications, PTMs），在染色质结构与功能调控中发挥关键作用。由于修饰类型繁杂且丰度动态跨度极广，对这类表观遗传标记进行精准定量始终是一项持续性的挑战。为此我们推出EpiProfile 2.0——本团队2015年发布的软件（v1.0）的扩展版本——可基于液相色谱-串联质谱（liquid chromatography–tandem mass spectrometry, LC–MS/MS）分析实现组蛋白肽段的精准定量。EpiProfile 2.0现已针对数据非依赖采集（data-independent acquisition, DIA）模式进行优化，通过前体离子与碎片离子提取离子色谱法精准刻画色谱峰形，并可区分肽段的同量异位形式。该软件采用基于分析样本训练得到的智能保留时间预测模型，可实现精准的峰识别与积分。EpiProfile 2.0支持无标记定量与同位素标记定量策略，适配多种模式生物，可识别疾病相关的已知序列突变，兼容多种衍生化方案，同时支持非常规翻译后修饰（如酰基衍生修饰）。综上，EpiProfile 2.0是一款通用且精准的基于LC–MS/MS分析的组蛋白修饰标记定量平台。作为同类首款专用软件，我们预期EpiProfile 2.0将在面向生物学与转化医学的表观遗传学研究中发挥基础性作用。该软件可通过https://github.com/zfyuan/EpiProfile2.0_Family免费获取与使用。