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Newbury, P.

Publications and source records attributed to Newbury, P..

2 recordsLinked to original sources

AICM: A Genuine Framework for Correcting Inconsistency Between Large Pharmacogenomics Datasets

The inconsistency of open pharmacogenomics datasets produced by different studies limits the usage of pharmacogenomics in biomarker discovery. Investigation of multiple pharmacogenomics datasets confirmed that the pairwise sensitivity data correlation between drugs, or rows, across different studies (drug-wise) is relatively low, while the pairwise sensitivity data correlation between cell-lines, or columns, across different studies (cell-wise) is considerably strong. This common interesting observation across multiple pharmacogenomics datasets suggests the existence of subtle consistency among the different studies (i.e., strong cell-wise correlation). However, significant noises are also shown (i.e., weak drug-wise correlation) and have prevented researchers from comfortably using the data directly. Motivated by this observation, we propose a novel framework for addressing the inconsistency between large-scale pharmacogenomics data sets. Our method can significantly boost the drug-wise correlation and can be easily applied to re-summarized and normalized datasets proposed by others. We also investigate our algorithm based on many different criteria to demonstrate that the corrected datasets are not only consistent, but also biologically meaningful. Eventually, we propose to extend our main algorithm into a framework, so that in the future when more data-sets become publicly available, our framework can hopefully offer a \"ground-truth\" guidance for references.

bioinformatics

Evaluating cancer cell lines as models for metastatic breast cancer

Metastasis is the most common cause of cancer-related death and, as such, there is an urgent need to discover new therapies to treat metastasized cancers. Cancer cell lines are widely-used models to study cancer biology and test drug candidates. However, it is still unknown to what extent they adequately resemble the disease in patients. The recent accumulation of large-scale genomic data in cell lines, mouse models, and patient tissue samples provides an unprecedented opportunity to evaluate the suitability of cell lines for metastatic cancer research. In this work, we used breast cancer as a case study. The comprehensive comparison of the genetic profiles of 57 breast cancer cell lines with those of metastatic breast cancer samples revealed substantial genetic differences. In addition, we identified cell lines that more closely resemble different subtypes of metastatic breast cancer. Surprisingly, a combined analysis of mutation, copy number variation and gene expression data suggested that MDA-MB-231, the most commonly used triple negative cell line for metastatic breast cancer research, had little genomic similarity with Basal-like metastatic breast cancer samples. We further compared cell lines with organoids, a new type of preclinical model which are becoming more popular in recent years. We found that organoids outperformed cell lines in resembling the transcriptome of metastatic breast cancer samples. However, additional differential expression analysis suggested that both types of models could not mimic the effects of tumor microenvironment and meanwhile had their own bias towards modeling specific biological processes. Our work provides a guide of cell line selection in metastasis-related study and sheds light on the potential of organoids in translational research.

bioinformatics