Biology subjects

Hong, J.

Publications and source records attributed to Hong, J..

5 recordsLinked to original sources

bioRxiv2018

Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice

High fructose intake is a major risk for metabolic syndrome; however, its effects seem to vary across individuals. To determine main factors involved in the inter-individual responses to fructose, we fed inbred mouse strains C57BL/6J (B6), DBA/2J (DBA) and FVB/NJ (FVB) with fructose. DBA mice showed the highest susceptibility to gain adiposity and glucose intolerance. Elevated insulin was found in DBA and FVB mice, and cholesterol levels were uniquely elevated in B6 mice. The transcriptional profiles of liver, hypothalamus, and adipose tissues showed strain- and tissue-specific pathways altered by fructose, such as fatty acid and cholesterol pathways for B6 and PPAR signaling for DBA in liver, and oxidative phosphorylation for B6 and protein processing for DBA in hypothalamus. Using network modeling, we predicted potential strain-specific key regulators of fructose response such as Fgf21 (DBA) and Lss (B6) in liver, and validated strain-biased responses as well as the regulatory actions of Fgf21 and Lss in primary hepatocytes. Our findings support that fructose perturbs individualized tissue networks and pathways and associates with distinct features of metabolic dysfunctions across genetically diverse mice. Our results elucidate the molecular pathways and gene regulatory mechanisms underlying inter-individual variability in response to high fructose diet.

systems biology↗

bioRxiv2018

Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 3,928 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci and highlighted a handful of candidate genes, many of which are specifically expressed in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.

genetics↗

bioRxiv2017

DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers

DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches.

cancer biology↗

bioRxiv2017

Adaptive Evolution Of Transcription Factor Binding Affinities

Understanding the molecular basis of gene expression evolution is a central problem in evolutionary biology. However, connecting changes in gene expression to increased fitness, and identifying the functional basis of those changes, remains challenging. To study adaptive evolution of gene expression in real time, we performed long term experimental evolution (LTEE) of Saccharomyces cerevisiae (budding yeast) in ammonium-limited chemostats. Following several hundred generations of continuous selection we found significant divergence of nitrogen-responsive gene expression in lineages with increased fitness. In multiple independent lineages we found repeated selection for non-synonymous mutations in the zinc finger DNA binding domain of the activating transcription factor (TF), GAT1, that operates within incoherent feedforward loops to control expression of the nitrogen catabolite repression (NCR) regulon. Missense mutations in the DNA binding domain of GAT1 reduce its binding affinity for the GATAA consensus sequence in a promoter-specific manner, resulting in increased expression of ammonium permease genes via both direct and indirect effects, thereby conferring increased fitness. We find that altered transcriptional output of the NCR regulon results in antagonistic pleiotropy in alternate environments and that the DNA binding domain of GAT1 is subject to purifying selection in natural populations. Our study shows that adaptive evolution of gene expression can entail tuning expression output by quantitative changes in TF binding affinities while maintaining the overall topology of a gene regulatory network.

evolutionary biology↗

bioRxiv2017

Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing

Quantitative analysis of next-generation sequencing data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are defined as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. The false positive rate of coordinate-based deduplication has not been well characterized and may introduce unforeseen biases during analyses. We developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed sequencing. Incorporation of UMIs enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TruSeq adapters containing UMIs (TrUMIseq adapters), we find that accurate removal of PCR duplicates results in enhanced data quality for quantitative analysis of allele frequencies in heterogeneous populations and gene expression.\n\nMethod SummaryTrUMIseq adapters incorporate unique molecular identifiers in TruSeq adapters while maintaining the capacity to multiplex sequencing libraries using existing workflows. The use of UMIs increases the accuracy of quantitative sequencing assays, including RNAseq and allele frequency estimation, by enabling accurate detection of PCR duplicates.

genomics↗