Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integra-tion methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bio-informatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.