Building Classification Models with Combined Biomarker Tests： Application to Early Detection of Liver Cancer

Early detection of hepatocellular carcinoma （HCC） is critical for the effective treatment. Alpha fetoprotein （AFP） serum level is currently used for HCC screening, but the cutoff of the AFP test has limited sensitivity （-50%）, indicating a high false negative rate. We have successfully demonstrated that cancer derived DNA biomarkers can be detected in urine of patients with cancer and can be used for the early detection of cancer （Jain et al., 2015; Lin et al., 2011; Song et al., 2012; Su, Lin, Song, ＆ Jain, 2014; Su, Wang, Norton, Brenner, ＆ Block, 2008）. By combining urine biomarkers （uBMK） values and serum AFP （sAFP） level, a new classification model has been proposed for more efficient HCC screening. Several criterions have been discussed to optimal the cutoff for uBMK score and sAFP score. A joint distribution of sAFP and uBMK with point mass has been fitted using maximum likelihood method. Numerical results show that the sAFP data and uBMK data are very well described by proposed model. A tree-structured sequential test can be optimized by selecting the cutoffs. Bootstrap simulations also show the robust classification results with the optimal cuto~..

Could wastewater analysis be a useful tool for China?——A review

Analysing wastewater samples is an innovative approach that overcomes many limitations of traditional surveys to identify and measure a range of chemicals that were consumed by or exposed to people living in a sewer catchment area. First conceptualised in 2001, much progress has been made to make wastewater analysis（WWA） a reliable and robust tool for measuring chemical consumption and/or exposure. At the moment, the most popular application of WWA, sometimes referred as sewage epidemiology, is to monitor the consumption of illicit drugs in communities around the globe, including China. The approach has been largely adopted by law enforcement agencies as a device to monitor the temporal and geographical patterns of drug consumption. In the future, the methodology can be extended to other chemicals including biomarkers of population health（e.g. environmental or oxidative stress biomarkers, lifestyle indicators or medications that are taken by different demographic groups） and pollutants that people are exposed to（e.g. polycyclic aromatic hydrocarbons,perfluorinated chemicals, and toxic pesticides）. The extension of WWA to a huge range of chemicals may give rise to a field called sewage chemical-information mining（SCIM） with unexplored potentials. China has many densely populated cities with thousands of sewage treatment plants which are favourable for applying WWA/SCIM in order to help relevant authorities gather information about illicit drug consumption and population health status. However, there are some prerequisites and uncertainties of the methodology that should be addressed for SCIM to reach its full potential in China.

A practical strategy to develop isoform-selective near-infrared fluorescent probes for human cytochrome P450 enzymes

Currently,the development of selective fluorescent probes toward targeted enzymes is still a great challenge,due to the existence of numerous isoenzymes that share similar catalytic capacity.Herein,a double-filtering strategy was established to effectively develop isoenzyme-specific fluorescent probe(s)for cytochrome P450(CYP)which are key enzymes involving in metabolism of endogenous substances and drugs.In the first-stage of our filtering approach,near-infrared(NIR)fluorophores with alkoxyl group were prepared for the screening of CYP-activated fluorescent substrates using a CYPs-dependent incubation system.In the second stage of our filtering approach,these candidates were further screened using reverse protein-ligand docking to effectively determine CYP isoenzyme-specific probe(s).Using our double-filtering approach,probes S9 and S10 were successfully developed for the real-time and selective detection of CYP2C9 and CYP2J2,respectively,to facilitate high-throughput screening and assessment of CYP2C9-mediated clinical drug interaction risks and CYP2J2-associated disease diagnosis.These observations suggest that our strategy could be used to develop the isoform-specific probes for CYPs.

Liquid biopsies:DNA methylation analyses in circulating cell-free DNA

Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.

A quick and effective multivariate statistical strategy for imaging mass spectrometry

A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry（IMS） techniques is reported.The strategy divides the whole datacube of the sample into several subsets and analyses them one by one to obtain the results.Instead of analyzing the whole datacube at one time,the strategy makes the analysis easier and decreases the computation time greatly.In this report,the IMS data are produced by the air flow-assisted ionization IMS（AFAI-IMS）.The strategy can be used in combination with most multivariate statistical analysis methods.In this paper,the strategy was combined with the principal component analysis（PCA） and partial least square analysis（PLS）.It was proven to be effective by analyzing the handwriting sample.By using the strategy,the m/z corresponding to the specific lipids in rat brain tissue were distinguished successfully.Moreover the analysis time grew linearly instead of exponentially as the size of sample increased.The strategy developed in this study has enormous potential for searching for the mjz of potential biomarkers quickly and effectively.