Feng Lin

Bio: Feng Lin is an academic researcher from Nanyang Technological University. The author has contributed to research in topics: Medicine & Plasmon. The author has an hindex of 23, co-authored 180 publications receiving 2195 citations. Previous affiliations of Feng Lin include Foshan University & Hebei University.

An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data

Abstract: Motivation: Epigenetic modifications are one of the critical factors to regulate gene expression and genome function. Among different epigenetic modifications, the differential histone modification sites (DHMSs) are of great interest to study the dynamic nature of epigenetic and gene expression regulations among various cell types, stages or environmental responses. To capture the histone modifications at whole genome scale, ChIP-seq technology is becoming a robust and comprehensive approach. Thus the DHMSs are potentially identifiable by comparing two ChIP-seq libraries. However, little has been addressed on this issue in literature. Results: Aiming at identifying DHMSs, we propose an approach called ChIPDiff for the genome-wide comparison of histone modification sites identified by ChIP-seq. Based on the observations of ChIP fragment counts, the proposed approach employs a hidden Markov model (HMM) to infer the states of histone modification changes at each genomic location. We evaluated the performance of ChIPDiff by comparing the H3K27me3 modification sites between mouse embryonic stem cell (ESC) and neural progenitor cell (NPC). We demonstrated that the H3K27me3 DHMSs identified by our approach are of high sensitivity, specificity and technical reproducibility. ChIPDiff was further applied to uncover the differential H3K4me3 and H3K36me3 sites between different cell states. Interesting biological discoveries were achieved from such comparison in our study. Availability: http://cmb.gis.a-star.edu.sg/ChIPSeq/tools.htm Contact:asflin@ntu.edu.sg; sungk@gis.a-star.edu.sg Supplementary information:Supplementary methods and data are available at Bioinformatics online.

A signal–noise model for significance analysis of ChIP-seq with negative control

Abstract: Motivation:ChIP-seq is becoming the main approach to the genome-wide study of protein–DNA interactions and histone modifications Existing informatics tools perform well to extract strong ChIP-enriched sites However, two questions remain to be answered: (i) to which extent is a ChIP-seq experiment able to reveal the weak ChIP-enriched sites? (ii) are the weak sites biologically meaningful? To answer these questions, it is necessary to identify the weak ChIP signals from background noise Results: We propose a linear signal–noise model, in which a noise rate was introduced to represent the fraction of noise in a ChIP library We developed an iterative algorithm to estimate the noise rate using a control library, and derived a library-swapping strategy for the false discovery rate estimation These approaches were integrated in a general-purpose framework, named CCAT (Control-based ChIP-seq Analysis Tool), for the significance analysis of ChIP-seq Applications to H3K4me3 and H3K36me3 datasets showed that CCAT predicted significantly more ChIP-enriched sites that the previous methods did With the high sensitivity of CCAT prediction, we revealed distinct chromatin features associated to the strong and weak H3K4me3 sites Availability: http://cmbgisa-staredusg/ChIPSeq/toolshtm Contact:sungk@gisa-staredusg; asflin@ntuedusg Supplementary Information:Supplementary data are available at Bioinformatics online

Direct observation of ultrafast plasmonic hot electron transfer in the strong coupling regime.

Abstract: Achieving strong coupling between plasmonic oscillators can significantly modulate their intrinsic optical properties. Here, we report the direct observation of ultrafast plasmonic hot electron transfer from an Au grating array to an MoS2 monolayer in the strong coupling regime between localized surface plasmons (LSPs) and surface plasmon polaritons (SPPs). By means of femtosecond pump-probe spectroscopy, the measured hot electron transfer time is approximately 40 fs with a maximum external quantum yield of 1.65%. Our results suggest that strong coupling between LSPs and SPPs has synergetic effects on the generation of plasmonic hot carriers, where SPPs with a unique nonradiative feature can act as an ‘energy recycle bin’ to reuse the radiative energy of LSPs and contribute to hot carrier generation. Coherent energy exchange between plasmonic modes in the strong coupling regime can further enhance the vertical electric field and promote the transfer of hot electrons between the Au grating and the MoS2 monolayer. Our proposed plasmonic strong coupling configuration overcomes the challenge associated with utilizing hot carriers and is instructive in terms of improving the performance of plasmonic opto-electronic devices. A device that taps into two types of surface plasmon waves offers new opportunities to transform light energy into speedy semiconductor charges. When surface plasmons are confined to nanoscale dimensions, they can rapidly decay and produce “hot” electrons with high kinetic energy. Zheyu Fang from Peking University in Beijing, China, and colleagues have constructed a metal–insulator–metal sandwich structure that improves harvesting of hot electrons for applications including photodetectors. To increase extraction under laser excitation, the team coated the insulator with an electron-attracting molybdenum disulfide monolayer. They also identified surface plasmon polaritons—mobile waves at the metal–insulator interface—in the sandwich structure using a gold grating with variable dimensions as the upper metal layer. Laser conditions that coupled mobile and localized plasmons promoted hot electron production instead of thermal dissipation.

Tailoring MoS2 Valley-Polarized Photoluminescence with Super Chiral Near-Field

Abstract: Transition metal dichalcogenides with intrinsic spin-valley degrees of freedom hold great potentials for applications in spintronic and valleytronic devices. MoS2 monolayer possesses two inequivalent valleys in the Brillouin zone, with each valley coupling selectively with circularly polarized photons. The degree of valley polarization (DVP) is a parameter to characterize the purity of valley-polarized photoluminescence (PL) of MoS2 monolayer. Usually, the detected values of DVP in MoS2 monolayer show achiral property under optical excitation of opposite helicities due to reciprocal phonon-assisted intervalley scattering process. Here, it is reported that valley-polarized PL of MoS2 can be tailored through near-field interaction with plasmonic chiral metasurface. The resonant field of the chiral metasurface couples with valley-polarized excitons, and tailors the measured PL spectra in the far-field, resulting in observation of chiral DVP of MoS2 -metasurface under opposite helicities excitations. Valley-contrast PL in the chiral heterostructure is also observed when illuminated by linearly polarized light. The manipulation of valley-polarized PL in 2D materials using chiral metasurface represents a viable route toward valley-polaritonic devices.

A Graph-Theoretical Approach for Tracing Filamentary Structures in Neuronal and Retinal Images

Abstract: The aim of this study is about tracing filamentary structures in both neuronal and retinal images. It is often crucial to identify single neurons in neuronal networks, or separate vessel tree structures in retinal blood vessel networks, in applications such as drug screening for neurological disorders or computer-aided diagnosis of diabetic retinopathy. Both tasks are challenging as the same bottleneck issue of filament crossovers is commonly encountered, which essentially hinders the ability of existing systems to conduct large-scale drug screening or practical clinical usage. To address the filament crossovers' problem, a two-step graph-theoretical approach is proposed in this paper. The first step focuses on segmenting filamentary pixels out of the background. This produces a filament segmentation map used as input for the second step, where they are further separated into disjointed filaments. Key to our approach is the idea that the problem can be reformulated as label propagation over directed graphs, such that the graph is to be partitioned into disjoint sub-graphs, or equivalently, each of the neurons (vessel trees) is separated from the rest of the neuronal (vessel) network. This enables us to make the interesting connection between the tracing problem and the digraph matrix-forest theorem in algebraic graph theory for the first time. Empirical experiments on neuronal and retinal image datasets demonstrate the superior performance of our approach over existing methods.

Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry

Abstract: A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

ChIP-Seq: advantages and challenges of a maturing technology

Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a technique for genome-wide profiling of DNA-binding proteins, histone modifications or nucleosomes. Owing to the tremendous progress in next-generation sequencing technology, ChIP-seq offers higher resolution, less noise and greater coverage than its array-based predecessor ChIP-chip. With the decreasing cost of sequencing, ChIP-seq has become an indispensable tool for studying gene regulation and epigenetic mechanisms. In this Review, I describe the benefits and challenges in harnessing this technique with an emphasis on issues related to experimental design and data analysis. ChIP-seq experiments generate large quantities of data, and effective computational analysis will be crucial for uncovering biological mechanisms.

a Quantum-Mechanical Theory of the Contribution of Excitons to the Complex Dielectric Constant of Crystals.

Abstract: It is shown that the ordinary semiclassical theory of the absorption of light by exciton states is not completely satisfactory (in contrast to the case of absorption due to interband transitions). A more complete theory is developed. It is shown that excitons are approximate bosons, and, in interaction with the electromagnetic field, the exciton field plays the role of the classical polarization field. The eigenstates of the system of crystal and radiation field are mixtures of photons and excitons. The ordinary one-quantum optical lifetime of an excitation is infinite. Absorption occurs only when "three-body" processes are introduced. The theory includes "local field" effects, leading to the Lorentz local field correction when it is applicable. A Smakula equation for the oscillator strength in terms of the integrated absorption constant is derived.

A clustering approach for identification of enriched domains from histone modification ChIP-Seq data

Abstract: Motivation: Chromatin states are the key to gene regulation and cell identity. Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) is increasingly being used to map epigenetic states across genomes of diverse species. Chromatin modification profiles are frequently noisy and diffuse, spanning regions ranging from several nucleosomes to large domains of multiple genes. Much of the early work on the identification of ChIP-enriched regions for ChIP-Seq data has focused on identifying localized regions, such as transcription factor binding sites. Bioinformatic tools to identify diffuse domains of ChIP-enriched regions have been lacking. Results: Based on the biological observation that histone modifications tend to cluster to form domains, we present a method that identifies spatial clusters of signals unlikely to appear by chance. This method pools together enrichment information from neighboring nucleosomes to increase sensitivity and specificity. By using genomic-scale analysis, as well as the examination of loci with validated epigenetic states, we demonstrate that this method outperforms existing methods in the identification of ChIP-enriched signals for histone modification profiles. We demonstrate the application of this unbiased method in important issues in ChIP-Seq data analysis, such as data normalization for quantitative comparison of levels of epigenetic modifications across cell types and growth conditions. Availability: http://home.gwu.edu/~wpeng/Software.htm Contact: [email protected] Supplementary information:Supplementary data are available at Bioinformatics online.