Fig 1.
Workflow of Cyclic Ordering with Feature Extraction (COFE).
Data without time labels are first optionally pre-filtered and then standardized. A novel cross-validation approach finds a value for the unknown sparsity parameter that guarantees good temporal ordering. Finally, COFE both assigns time labels to the samples and produces a list of rhythmic features in the data.
Fig 2.
Circadian population rhythms in human adenocarcinomas (ACs).
(A) Demographics of patients, whose biosamples provided data for training COFE. (B) Number of rhythmic genes and rhythmic core clock genes identified in each AC. (C) Cumulative distribution of the rhythmic gene amplitudes in different ACs. (D) Consensus amplitude and peak times of 15 commonly expressed core clock genes across the ACs (left). The dispersion of peak times of clock genes from the consensus arrangement across the ACs (middle). The relative strength of core clock network in different ACs (right). (E) Intersection of rhythmic gene sets across 11, 10 and 9 different ACs. (F) Reactome-based gene-set enrichment analysis of the common rhythmic genes. (G) Variability of peak times of genes within a pathway compared against the variability of peak times with respect to the core clock in different ACs. The data underlying Figure panels can be found in S1 Data.
Fig 3.
Coupling of the circadian clock to the cell cycle and the proteome.
(A) Distribution of predicted time labels for the samples in each AC. (B) Difference in time labels predicted by COFE between cancer and patient-matched healthy samples, where both are available. (C) Scores for cell cycle phases (S and G2/M) in the different ACs. The raw and LOESS-smoothed scores per sample are shown. (D) The number of rhythmic and total measured proteins in each AC. (E) The amplitude of rhythmic protein expression (color coded as in (A)) for proteins including modified forms that are rhythmic in at least 10 of the 11 ACs. (F) The raw data and LOESS-smoothed means for the rhythmic protein with the highest amplitude in each AC. (G) Distribution of the difference in peak times of expression of rhythmic proteins and their corresponding rhythmic gene. The data underlying Figure panels can be found in S1 Data.
Fig 4.
Rhythmic targets of FDA-approved and clinical candidate cancer drugs.
The -fold amplitude (A) and peak time relative to the core clock (B) of the largest rhythmic target gene in each AC of FDA approved and clinical candidate drugs that target cancer pathways or processes. All FDA-approved drugs and clinical candidates with rhythmic targets in at least 7 ACs are included. Drugs with multiple rhythmic gene targets in an AC are boxed in black. The data underlying Figure panels can be found in S1 Data.