Apolipoprotein E Gene Revisited: Contribution of Rare Variants to Alzheimer's Disease Susceptibility in Southern Chinese.

Background: APOE ε4 is the best-known risk factor for late-onset alzheimer's disease (AD). Population studies have demonstrated a relatively low prevalence of APOE ε4 among Chinese population, implying additional risk factors that are Chinese-specific may exist. Apart from - alleles, genetic variation profile along the full-length APOE has rarely been investigated.

Population-Wide Genetic Risk Prediction of Complex Diseases: A Pilot Feasibility Study in Macau Population for Precision Public Healthcare Planning.

The genetic bases of many common diseases have been identified through genome-wide association studies in the past decade. However, the application of this approach on public healthcare planning has not been well established. Using Macau with population of around 650,000 as a basis, we conducted a pilot study to evaluate the feasibility of population genomic research and its potential on public health decisions.

Novel structural co-expression analysis linking the NPM1-associated ribosomal biogenesis network to chronic myelogenous leukemia.

Co-expression analysis reveals useful dysregulation patterns of gene cooperativeness for understanding cancer biology and identifying new targets for treatment. We developed a structural strategy to identify co-expressed gene networks that are important for chronic myelogenous leukemia (CML). This strategy compared the distributions of expressional correlations between CML and normal states, and it identified a data-driven threshold to classify strongly co-expressed networks that had the best coherence with CML.

Current and future molecular diagnostics in non-small-cell lung cancer.

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients.

DECODE: an integrated differential co-expression and differential expression analysis of gene expression data.

Background: Both differential expression (DE) and differential co-expression (DC) analyses are appreciated as useful tools in understanding gene regulation related to complex diseases. The performance of integrating DE and DC, however, remains unexplored.

Results: In this study, we proposed a novel analytical approach called DECODE (Differential Co-expression and Differential Expression) to integrate DC and DE analyses of gene expression data.

Coexpression Pattern Analysis of NPM1-Associated Genes in Chronic Myelogenous Leukemia.

Background: Nucleophosmin 1 (NPM1) plays an important role in ribosomal synthesis and malignancies, but NPM1 mutations occur rarely in the blast-crisis and chronic-phase chronic myelogenous leukemia (CML) patients. The NPM1-associated gene set (GCM_NPM1), in total 116 genes including NPM1, was chosen as the candidate gene set for the coexpression analysis. We wonder if NPM1-associated genes can affect the ribosomal synthesis and translation process in CML.

Gene network exploration of crosstalk between apoptosis and autophagy in chronic myelogenous leukemia.

Background: Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses.

Novel approach for coexpression analysis of E2F1-3 and MYC target genes in chronic myelogenous leukemia.

Background: Chronic myelogenous leukemia (CML) is characterized by tremendous amount of immature myeloid cells in the blood circulation. E2F1-3 and MYC are important transcription factors that form positive feedback loops by reciprocal regulation in their own transcription processes. Since genes regulated by E2F1-3 or MYC are related to cell proliferation and apoptosis, we wonder if there exists difference in the coexpression patterns of genes regulated concurrently by E2F1-3 and MYC between the normal and the CML states.

Maternal plasma RNA sequencing for genome-wide transcriptomic profiling and identification of pregnancy-associated transcripts.

Background: Analysis of circulating RNA in the plasma of pregnant women has the potential to serve as a powerful tool for noninvasive prenatal testing and research. However, detection of circulating RNA in the plasma in an unbiased and high-throughput manner has been technically challenging. Therefore, only a limited number of circulating RNA species in maternal plasma have been validated as pregnancy- and placenta-specific biomarkers.

Investigation of biological factors influencing the placental mRNA profile in maternal plasma.

Objective: Circulating placental-derived RNA is useful for noninvasive prenatal investigation. However, in addition to placental gene expression, there are limited investigations on other biological parameters that may affect the circulating placental RNA profile. In this study, we explored two of these potential parameters.

Advanced technologies for studying circulating tumor cells at the protein level.

Metastasis is the main cause of cancer death. As the tumor progresses, cells from the primary tumor site are shed into the bloodstream as circulating tumor cells (CTCs). Eventually, these cells colonize other organs and form distant metastases.

High resolution size analysis of fetal DNA in the urine of pregnant women by paired-end massively parallel sequencing.

Background: Fetal DNA in maternal urine, if present, would be a valuable source of fetal genetic material for noninvasive prenatal diagnosis. However, the existence of fetal DNA in maternal urine has remained controversial. The issue is due to the lack of appropriate technology to robustly detect the potentially highly degraded fetal DNA in maternal urine.

Recent advances in the analysis of fetal nucleic acids in maternal plasma.

Purpose Of Review: Noninvasive prenatal diagnosis can be achieved by analyzing cell-free fetal DNA in maternal plasma. The fact that circulating fetal DNA represents only a minor fraction of the DNA that is present in maternal plasma has presented analytical challenges for a number of applications. In this review, we discuss such challenges and how they have been resolved by recent developments in the field.

Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA.

Hemophilia is a bleeding disorder with X-linked inheritance. Current prenatal diagnostic methods for hemophilia are invasive and pose a risk to the fetus. Cell-free fetal DNA analysis in maternal plasma provides a noninvasive mean of assessing fetal sex in such pregnancies.

Synergy of total PLAC4 RNA concentration and measurement of the RNA single-nucleotide polymorphism allelic ratio for the noninvasive prenatal detection of trisomy 21.

Background: Maternal plasma mRNA encoded by the PLAC4 gene (placenta-specific 4), which is transcribed from chromosome 21 in placental cells, is a potential marker for the noninvasive assessment of chromosome 21 dosage in the fetus. We evaluated the diagnostic sensitivities and specificities of 2 trisomy 21-screening approaches that use maternal plasma PLAC4 mRNA.

Methods: We studied maternal plasma samples from 153 pregnant women carrying euploid and trisomy 21 fetuses.

Non-invasive prenatal detection of fetal trisomy 18 by RNA-SNP allelic ratio analysis using maternal plasma SERPINB2 mRNA: a feasibility study.

Objective: Non-invasive prenatal diagnosis of chromosome aneuploidies has been achieved by measuring the ratio of two alleles of a single nucleotide polymorphism (SNP) in circulating placental mRNA (the RNA-SNP allelic ratio approach) in maternal plasma. We investigated the feasibility of applying this approach for the non-invasive prenatal detection of fetal trisomy 18.

Method: We targeted serpin peptidase inhibitor, clade B (ovalbumin), membrane 2 (SERPINB2) mRNA, which is transcribed from chromosome 18 and is preferentially expressed by the placenta.

Placenta-derived fetal specific mRNA is more readily detectable in maternal plasma than in whole blood.

Background: Placental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis.

Methodology: The concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis.

Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma.

Chromosomal aneuploidy is the major reason why couples opt for prenatal diagnosis. Current methods for definitive diagnosis rely on invasive procedures, such as chorionic villus sampling and amniocentesis, and are associated with a risk of fetal miscarriage. Fetal DNA has been found in maternal plasma but exists as a minor fraction among a high background of maternal DNA.

Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma.

Prenatal diagnosis of monogenic diseases, such as cystic fibrosis and beta-thalassemia, is currently offered as part of public health programs. However, current methods based on chorionic villus sampling and amniocentesis for obtaining fetal genetic material pose a risk to the fetus. Since the discovery of cell-free fetal DNA in maternal plasma, the noninvasive prenatal assessment of paternally inherited traits or mutations has been achieved.

Presence of donor-derived DNA and cells in the urine of sex-mismatched hematopoietic stem cell transplant recipients: implication for the transrenal hypothesis.

Background: The term "transrenal DNA" was coined in 2000 to signify that DNA in urine may come from the passage of plasma DNA through the kidney barrier. Although DNA in the urine has the potential to provide a completely noninvasive source of nucleic acids for molecular diagnosis, its existence remains controversial.

Methods: We obtained blood and urine samples from 22 hematopoietic stem cell transplant (HSCT) recipients and used fluorescence in situ hybridization, PCR for short tandem repeats, mass spectrometry, quantitative PCR, and immunofluorescence detection to study donor-derived DNA in the urine.

A microarray approach for systematic identification of placental-derived RNA markers in maternal plasma.

Circulating fetal RNA in maternal plasma has offered a new approach for noninvasive prenatal diagnosis and monitoring. Circulating fetal RNA markers could potentially be used for all pregnant women without being limited by fetal-maternal genetic polymorphisms and fetal gender. Over the past few years, encouraging findings have been reported on the detection and possible clinical applications of circulating fetal RNA.

Digital PCR for the molecular detection of fetal chromosomal aneuploidy.

Trisomy 21 is the most common reason that women opt for prenatal diagnosis. Conventional prenatal diagnostic methods involve the sampling of fetal materials by invasive procedures such as amniocentesis. Screening by ultrasonography and biochemical markers have been used to risk-stratify pregnant women before definitive invasive diagnostic procedures.