posted on 2022-05-12, 07:11authored byYing Zhu, Qingce Zang, Zhigang Luo, Jiuming He, Ruiping Zhang, Zeper Abliz
Rapid and accurate metabolite annotation
in mass spectrometry imaging
(MSI) can improve the efficiency of spatially resolved metabolomics
studies and accelerate the discovery of reliable in situ disease biomarkers. To date, metabolite annotation tools in MSI
generally utilize isotopic patterns, but high-throughput fragmentation-based
identification and biological and technical factors that influence
structure elucidation are active challenges. Here, we proposed an
organ-specific, metabolite-database-driven approach to facilitate
efficient and accurate MSI metabolite annotation. Using data-dependent
acquisition (DDA) in liquid chromatography coupled with tandem mass
spectrometry (LC–MS/MS) to generate high-coverage product ions,
we identified 1620 unique metabolites from eight mouse organs (brain,
liver, kidney, heart, spleen, lung, muscle, and pancreas) and serum.
Following the evaluation of the adduct form difference of metabolite
ions between LC–MS and airflow-assisted desorption electrospray
ionization (AFADESI)-MSI and deciphering organ-specific metabolites,
we constructed a metabolite database for MSI consisting of 27,407
adduct ions. An automated annotation tool, MSIannotator, was then
created to conduct metabolite annotation in the MSI dataset with high
efficiency and confidence. We applied this approach to profile the
spatially resolved landscape of the whole mouse body and discovered
that metabolites were distributed across the body in an organ-specific
manner, which even spanned different mouse strains. Furthermore, the
spatial metabolic alteration in diabetic mice was delineated across
different organs, exhibiting that differentially expressed metabolites
were mainly located in the liver, brain, and kidney, and the alanine,
aspartate, and glutamate metabolism pathway was simultaneously altered
in these three organs. This approach not only enables robust metabolite
annotation and visualization on a body-wide level but also provides
a valuable database resource for underlying organ-specific metabolic
mechanisms.