Inferring evolutionary trajectories from cross-sectional transcriptomic data to mirror lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased.

Predicting the progression of mild cognitive impairment to Alzheimer's disease by longitudinal magnetic resonance imaging-based dictionary learning.

OBJECTIVE: Efficient prediction of the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is important for the early intervention and management of AD. The aim of our study was to develop a longitudinal structural magnetic resonance imaging-based prediction system for MCI progression. METHODS: A total of 164 MCI patients with longitudinal data were collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI). After preprocessing, a discriminative dictionary learning framework was applied to differentiate MCI patches, avoiding the segmentation of regions of interest. Then, the proportion of patches classified as more severe atrophy patches in a patient was calculated as his or her feature to be input into a simple support vector machine. Finally, a new subject was predicted with fourfold cross-validation (CV), and the area under the receiver operating characteristic curve (AUC) was determined. RESULTS: The average accuracy and AUC values after fourfold CV were 0.973 and 0.984, respectively. The effects of the data from one or two time points were also investigated. CONCLUSION: The proposed prediction system achieves desirable and reliable performance in predicting progression for MCI patients. Additionally, the prediction of MCI progression with longitudinal data was more effective and accurate. SIGNIFICANCE: The developed scheme is expected to advance the clinical research and treatment of MCI patients.