In the past decade, significant progress has been made in complex disease research across multiple omics layers from genome, transcriptome and proteome to metabolome. There is an increasing awareness of the importance of biological interconnections, and much success has been achieved using systems biology approaches. However, because of the typical focus on one single omics layer at a time, existing systems biology findings explain only a modest portion of complex disease. Recent advances in multi-omics data collection and sharing present us new opportunities for studying complex diseases in a more comprehensive fashion, and yet simultaneously create new challenges considering the unprecedented data dimensionality and diversity. Here, our goal is to review extant and emerging network approaches that can be applied across multiple biological layers to facilitate a more comprehensive and integrative multilayered omics analysis of complex diseases.

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Summary Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. Intriguingly, some bile acids measured in brain tissue cannot be explained by the presence of enzymes responsible for their synthesis, suggesting that they may originate from the gut microbiome and are transported to the brain. These findings motivate further research into bile acid metabolism in AD to elucidate their possible connection to cognitive decline.

Soil organic matter (SOM) is the main source of soil nutrients, which are essential for the growth and development of agricultural crops. Hyperspectral remote sensing is one of the most efficient ways of estimating the SOM content. Visible, near infrared, and mid-infrared reflectance spectroscopy, combined with the partial least squares regression (PLSR) method is considered to be an effective way of determining soil properties. In this study, we used 54 different spectral pretreatments to preprocess soil spectral data. These spectral pretreatments were composed of three denoising methods, six data transformations, and three dimensionality reduction methods. The three denoising methods included no denoising (ND), Savitzky–Golay denoising (SGD), and wavelet packet denoising (WPD). The six data transformations included original spectral data, R; reciprocal, 1/R; logarithmic, log(R); reciprocal logarithmic, log(1/R); first derivative, R’; and first derivative of reciprocal, (1/R)’. The three dimensionality reduction methods included no dimensionality reduction (NDR), sensitive waveband dimensionality reduction (SWDR), and principal component analysis (PCA) dimensionality reduction (PCADR). The processed spectra were then employed to construct PLSR models for predicting the SOM content. The main results were as follows—(1) the wavelet packet denoising (WPD)-R’ and WPD-(1/R)’ data showed stronger correlations with the SOM content. Furthermore, these methods could effectively limit the correlation between the adjacent bands and, thus, prevent “overfitting”. (2) Of the 54 pretreatments investigated, WPD-(1/R)’-PCADR yielded the model with the highest accuracy and stability. (3) For the same denoising method and spectral transformation data, the accuracy of the SOM content estimation model based on SWDR was higher than that of the model based on NDR. Furthermore, the accuracy in the case of PCADR was higher than that for SWDR. (4) Dimensionality reduction was effective in preventing data overfitting. (5) The quality of the spectral data could be improved and the accuracy of the SOM content estimation model could be enhanced effectively, by using some appropriate preprocessing methods (one combining WPD and PCADR in this study).