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Lam, W.

Publications and source records attributed to Lam, W..

2 recordsLinked to original sources

Radiomics Analysis Using Stability Selection Supervised Principal Component Analysis for Right-censored Survival Data

Radiomics is a newly emerging field that involves the extraction of a large number of quantitative features from biomedical images through the use of data-characterization algorithms. Radiomics provides a noninvasive approach for personalized therapy decision by identifying distinctive imaging features for predicting prognosis and therapeutic response. So far, many of the published radiomics studies utilize existing out of the box algorithms to identify the prognostic markers from biomedical images that are not specific to radiomics data. T o better utilize biomedical image, we propose a novel machine learning approach, stability selection supervised principal component analysis (SSSuperPCA) that identify a set of stable features from radiomics big data coupled with dimension reduction for right censored survival outcomes. In this paper, we describe stability selection supervised principal component analysis for radiomics data with right-censored survival outcomes. The proposed approach allows us to identify a set of stable features that are highly associated with the survival outcomes, control the per-family error rate, and predict the survival in a simple yet meaningful manner. We evaluate the performance of SSSuperPCA using simulations and real data sets for non-small cell lung cancer and head and neck cancer, and compare it with other machine learning algorithms. The results demonstrate that our method has a competitive edge over other existing methods in identifying the prognostic markers from biomedical big imaging data for the prediction of right-censored survival outcomes. An R package SSSuperPCA is available at the website: http://web.hku.hk/[~]herbpang/SSSuperPCA.html

bioinformatics

The contribution of non-canonical splicing mutations to severe dominant developmental disorders

Mutations which perturb normal pre-mRNA splicing are significant contributors to human disease. We used exome sequencing data from 7,833 probands with developmental disorders (DD) and their unaffected parents, as well as >60,000 aggregated exomes from the Exome Aggregation Consortium, to investigate selection around the splice site, and quantify the contribution of splicing mutations to DDs. Patterns of purifying selection, a deficit of variants in highly constrained genes in healthy subjects and excess de novo mutations in patients highlighted particular positions within and around the consensus splice site of greater functional relevance. Using mutational burden analyses in this large cohort of proband-parent trios, we could estimate in an unbiased manner the relative contributions of mutations at canonical dinucleotides (73%) and flanking non-canonical positions (27%), and calculated the positive predictive value of pathogenicity for different classes of mutations. We identified 18 patients with likely diagnostic de novo mutations in dominant DD-associated genes at non-canonical positions in splice sites. We estimate 35-40% of pathogenic variants in non-canonical splice site positions are missing from public databases.

genetics