A patient-specific functional module and path identification technique from RNA-seq data.

With the advancement of new technologies, a huge amount of high dimensional data is being generated which is opening new opportunities and challenges to the study of cancer and diseases. In particular, distinguishing the patient-specific key components and modules which drive tumorigenesis is necessary to analyze. A complex disease generally does not initiate from the dysregulation of a single component but it is the result of the dysfunction of a group of components and networks which differs from patient to patient. However, a patient-specific network is required to understand the disease and its molecular mechanism. We address this requirement by constructing a patient-specific network by sample-specific network theory with integrating cancer-specific differentially expressed genes and elite genes. By elucidating patient-specific networks, it can identify the regulatory modules, driver genes as well as personalized disease networks which can lead to personalized drug design. This method can provide insight into how genes are associating with each other and characterized the patient-specific disease subtypes. The results show that this method can be beneficial for the detection of patient-specific differential modules and interaction between genes. Extensive analysis using existing literature, gene enrichment and survival analysis for three cancer types STAD, PAAD and LUAD shows the effectiveness of this method over other existing methods. In addition, this method can be useful for personalized therapeutics and drug design. This methodology is implemented in the R language and is available at https://github.com/riasatazim/PatientSpecificRNANetwork.

CDSImpute: An ensemble similarity imputation method for single-cell RNA sequence dropouts.

BACKGROUND: Single-cell RNA-sequencing enables the opportunity to investigate cell heterogeneity, discover new types of cells and to perform transcriptomic reconstruction at a single-cell resolution. Due to technical inadequacy, the presence of dropout events hinders the downstream and differential expression analysis. Therefore, it demands an efficient and accurate approach to recover the true gene expression. To fill the gap, we present a novel Single-cell RNA dropout imputation method to retrieve the original gene expression of the genes with excessive zero and near-zero counts. RESULT: Here we have developed CDSImpute (Correlation Distance Similarity Imputation) to identify dropouts induced in scRNA-seq data rather than biological zeros and recover true gene expression. By taking into consideration correlation and negative distance between cells, a similar cell list has been created and by borrowing the gene expression from similar cells dropout has been detected and corrected simultaneously. The improvement is consistent with simulation data and several publicly available scRNA-seq datasets. The clustering accuracy of CDSImpute is evaluated by adjusted rand index on Kolod, Pollen and Usoskin datasets are 1.00, 0.79 and 0.34 respectively. CDSImpute achieves improved performance compared to the three existing methods evaluated by precise cell-type identification and differentially expressed gene detection from scRNA-seq Data. CONCLUSION: CDSImpute is a novel effective method to impute the dropout events of a scRNA-seq expression matrix. The package is implemented in the R language and is available at https://github.com/riasatazim/CDSImpute.