High-resolution emission inventory of biogenic volatile organic compounds for rapidly urbanizing areas: A case of Shenzhen megacity, China.

The effects of volatile organic compounds on urban air quality and the ozone have been widely acknowledged, and the contributions of relevant biogenic sources are currently receiving rising attentions. However, inventories of biogenic volatile organic compounds (BVOCs) are in fact limited for the environmental management of megacities. In this study, we provided an estimation of BVOC emissions and their spatial characteristics in a typical urbanized area, Shenzhen megacity, China, based on an in-depth vegetation investigation and using remote sensing data. The total BVOC emission in Shenzhen in 2019 was estimated to be 3.84 × 109 g C, of which isoprene contributed to about 24.4%, monoterpenes about 44.4%, sesquiterpenes about 1.9%, and other VOCs (OVOCs) about 29.3%. Metropolitan BVOC emissions exhibited a seasonal pattern with a peak in July and a decline in January. They were mainly derived from the less built-up areas (88.9% of BVOC emissions). Estimated BVOCs comprised around 5.2% of the total municipal VOC emissions in 2019. This percentage may increase as more green spaces emerge and anthropogenic emissions decrease in built-up areas. Furthermore, synergistic effects existed between BVOC emissions and relevant vegetation-based ecosystem services (e.g., air purification, carbon fixation). Greening during urban sprawl should be based on a trade-off between BVOC emissions and ecosystem benefits of urban green spaces. The results suggested that urban greening in Shenzhen, and like other cities as well, need to account for BVOC contributions to ozone. Meanwhile, greening cites should adopt proactive environmental management by using plant species with low BVOC emissions to maintain urban ecosystem services while avoid further degradation to ozone pollution.

Lotus Leaf Derived NiS/Carbon Nanofibers/Porous Carbon Heterogeneous Structures for Strong and Broadband Microwave Absorption.

Developing composite materials with the synergistic effects of heterogeneous structures and multiple components is considered as a promising strategy to achieve high-performance electromagnetic wave (EMW) absorbers. To further satisfy the demand of broadband and strong microwave absorption, a novel NiS/carbon nanofibers (CNFs)/porous carbon composite is successfully synthesized by hydrothermal and chemical vapor deposition using lotus leaves as a biomass carbon source. A few carbon nanotubes (CNTs) and uniformly dispersed Ni nanocrystals have also been found in the hybrid. Benefiting from the porous structure derived from lotus leaves, the combination of dielectric NiS, conductive carbon nanomaterials, and magnetic Ni nanoparticles, together with the three-dimensional conductive network of CNFs and CNTs, the remarkable EMW absorption properties with a minimum reflection loss up to -67.65 dB have been achieved at merely 2.32 mm. Besides, the widest effective absorption band can reach 5.9 GHz with a thin thickness of 2.07 mm, covering almost the entire Ku band. In addition, under the incident angle of 31°, the radar cross-section reduction value of LNSF-600 can reach 42.88 dBm2. Therefore, this work provides an efficient and facile method for manufacturing outstanding biomass-derived EMW absorbers.

Genomic Characterization Revealed PM2.5-Associated Mutational Signatures in Lung Cancer Including Activation of APOBEC3B.

Fine particulate matter (PM2.5) exposure causes DNA mutations and abnormal gene expression leading to lung cancer, but the detailed mechanisms remain unknown. Here, analysis of genomic and transcriptomic changes upon a PM2.5 exposure-induced human bronchial epithelial cell-based malignant transformed cell model in vitro showed that PM2.5 exposure led to APOBEC mutational signatures and transcriptional activation of APOBEC3B along with other potential oncogenes. Moreover, by analyzing mutational profiles of 1117 non-small cell lung cancers (NSCLCs) from patients across four different geographic regions, we observed a significantly higher prevalence of APOBEC mutational signatures in non-smoking NSCLCs than smoking in the Chinese cohorts, but this difference was not observed in TCGA or Singapore cohorts. We further validated this association by showing that the PM2.5 exposure-induced transcriptional pattern was significantly enriched in Chinese NSCLC patients compared with other geographic regions. Finally, our results showed that PM2.5 exposure activated the DNA damage repair pathway. Overall, here we report a previously uncharacterized association between PM2.5 and APOBEC activation, revealing a potential molecular mechanism of PM2.5 exposure and lung cancer.

Advances in spring leaf phenology are mainly triggered by elevated temperature along the rural-urban gradient in Beijing, China.

Urbanization-induced phenological changes have received considerable attention owing to their implications for determining urban ecosystem productivity and predicting the response of plants and ecosystem carbon cycles to future climate change. However, inconsistent rural-urban gradients in plant phenology remain, and phenological drivers other than temperature are poorly understood. In this study, we simultaneously observed the micro-climate and spring leaf phenology of seven woody plant species at 13 parks along a rural-urban gradient in Beijing, China. The minimum (Tmin) and mean (Tmean) air temperature and the minimum (VPDmin) and mean (VPDmean) vapor pressure deficit increased significantly along the rural-urban gradient, but the maximum air temperature (Tmax) and maximum vapor pressure deficit (VPDmax) did not. All observed leaf phenological phases for the seven species were significantly advanced along the rural-urban gradient by 0.20 to 1.02 days/km. Advances in the occurrence of leaf phenological events were significantly correlated with increases in Tmean (accounting for 57-59% variation), Tmin (21-26%), VPDmin (12-16%), and VPDmean (3-5%), but not with changes in Tmax or VPDmax. Advances in spring leaf phenology along the rural-urban gradient differed between non-native species and native species and between shrubs and trees. The reason may be mainly that the sensitivities of spring leaf phenology to micro-climate differ with species origin and growth form. This study highlights that urbanization-induced increases in Tmean and Tmin are the major contributors to advances in spring leaf phenology along the rural-urban gradient, exerting less influence on native species than on non-native species.

Effect of Microstructures of Carbon Nanoproducts Grown on Carbon Fibers on the Interfacial Properties of Epoxy Composites.

Two kinds of carbon nanoproducts with different microstructures, namely, carbon nanotubes (CNTs) and carbon nanofibers (CNFs), were grown on the surface of carbon fibers (CFs) by chemical vapor deposition (CVD) at low temperatures to improve the interface bonding between fibers and resins. The short-beam method and the micro-debonding method were used to test the interlaminar shear strength (ILSS) and interfacial shear strength (IFSS) of the composites. The results showed that the contribution of CNTs to the improvement of interfacial properties was better than that of CNFs. Specifically, the ILSS and IFSS of the CF-CNFs/epoxy composites increased by 18.59 and 24.39%, respectively, while the ILSS and IFSS of the CF-CNTs/epoxy composites increased by 26.97 and 47.79%, respectively. Compared with CNFs, the high degree of graphitization of CNTs and the π-interactions with the resin can better induce the formation of an interphase between the fiber and the resin, which suppressed the initiation of cracks and extended the propagation path of the cracks in the composites.

Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.

Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases.

Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.

Asf1/HIRA facilitate global histone deacetylation and associate with HP1 to promote nucleosome occupancy at heterochromatic loci.

Heterochromatin impacts various nuclear processes by providing a recruiting platform for diverse chromosomal proteins. In fission yeast, HP1 proteins Chp2 and Swi6, which bind to methylated histone H3 lysine 9, associate with SHREC (Snf2/HDAC repressor complex) and Clr6 histone deacetylases (HDACs) involved in heterochromatic silencing. However, heterochromatic silencing machinery is not fully defined. We describe a histone chaperone complex containing Asf1 and HIRA that spreads across silenced domains via its association with Swi6 to enforce transcriptional silencing. Asf1 functions in concert with a Clr6 HDAC complex to silence heterochromatic repeats, and it suppresses antisense transcription by promoting histone deacetylation. Furthermore, we demonstrate that Asf1 and SHREC facilitate nucleosome occupancy at heterochromatic regions but TFIIIC transcription factor binding sites within boundary elements are refractory to these factors. These analyses uncover a role for Asf1 in global histone deacetylation and suggest that HP1-associated histone chaperone promotes nucleosome occupancy to assemble repressive heterochromatin.

Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs.

Eukaryotic transcriptomes are characterized by widespread transcription of noncoding and antisense RNAs, which is linked to key chromosomal processes, such as chromatin remodelling, gene regulation and heterochromatin assembly. However, these transcripts can be deleterious, and their accumulation is suppressed by several mechanisms including degradation by the nuclear exosome. The mechanisms by which cells differentiate coding RNAs from transcripts targeted for degradation are not clear. Here we show that the variant histone H2A.Z, which is loaded preferentially at the 5' ends of genes by the Swr1 complex containing a JmjC domain protein, mediates suppression of antisense transcripts in the fission yeast Schizosaccharomyces pombe genome. H2A.Z is partially redundant in this regard with the Clr4 (known as SUV39H in mammals)-containing heterochromatin silencing complex that is also distributed at euchromatic loci, and with RNA interference component Argonaute (Ago1). Loss of Clr4 or Ago1 alone has little effect on antisense transcript levels, but cells lacking either of these factors and H2A.Z show markedly increased levels of antisense RNAs that are normally degraded by the exosome. These analyses suggest that as well as performing other functions, H2A.Z is a component of a genome indexing mechanism that cooperates with heterochromatin and RNAi factors to suppress read-through antisense transcripts.

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination.

Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3-M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recombination-promoting complex (RPC) containing Swi2 and Swi5. In P cells, the RPC localizes to a specific DNA element located adjacent to mat3, but in M cells it spreads across the silent mating-type region, including mat2-P. This differential distribution of the RPC regulates nonrandom choice of donors. However, cell-type-specific differences in RPC localization are not understood. Here we show that the mat1-M-encoded factor Mc, which shares structural and functional similarities with the male sex-determining factor SRY, is highly enriched at the swi2 and swi5 loci and promotes elevated levels of RPC components. Loss of Mc reduces Swi2 and Swi5 to levels comparable to those in P cells and disrupts RPC spreading across the mat2/3 region. Mc also localizes to loci expressed preferentially in M cells and to retrotransposon LTRs. We demonstrate that Mc localization at LTRs and at swi2 requires Abp1, a homolog of transposon-derived CENP-B protein and that loss of Abp1 impairs Swi2 protein expression and the donor choice mechanism. These results suggest that Mc modulates levels of recombination factors, which is important for mating-type donor selection and for the biased gene conversion observed during meiosis, where M cells serve as preferential donors of genetic information.

A molecular mechanism for embryonic resetting of winter memory and restoration of winter annual growth habit in wheat.

The staple food crop winter bread wheat (Triticum aestivum) acquires competence to flower in late spring after experiencing prolonged cold in temperate winter seasons, through the physiological process of vernalization. Prolonged cold exposure results in transcriptional repression of the floral repressor VERNALIZATION 2 (TaVRN2) and activates the expression of the potent floral promoter VERNALIZATION 1 (TaVRN1). Cold-induced TaVRN1 activation and TaVRN2 repression are maintained in post-cold vegetative growth and development, leading to an epigenetic 'memory of winter cold', enabling spring flowering. When and how the cold memory is reset in wheat is essentially unknown. Here we report that the cold-induced TaVRN1 activation is inherited by early embryos, but reset in subsequent embryo development, whereas TaVRN2 remains silenced through seed development, but is reactivated rapidly by light during seed germination. We further found that a chromatin reader mediates embryonic resetting of TaVRN1 and that chromatin modifications play an important role in the regulation of TaVRN1 expression and thus the floral transition, in response to developmental state and environmental cues. The findings define a two-step molecular mechanism for re-establishing vernalization requirement in common wheat, ensuring that each generation must experience winter cold to acquire competence to flower in spring.

Novel molecular subtypes of intracranial germ cell tumors expand therapeutic opportunities.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumors (NGGCTs). Previous studies have found that somatic mutations involving the mitogen-activated protein kinase/mTOR signaling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking. METHODS: We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing. RESULTS: We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: Immune-hot, MYC/E2F, and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signaling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumors showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs. CONCLUSIONS: Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.

Large area single crystal gold of single nanometer thickness for nanophotonics.

Two-dimensional single crystal metals, in which the behavior of highly confined optical modes is intertwined with quantum phenomena, are highly sought after for next-generation technologies. Here, we report large area (>104 µm2), single crystal two-dimensional gold flakes (2DGFs) with thicknesses down to a single nanometer level, employing an atomic-level precision chemical etching approach. The decrease of the thickness down to such scales leads to the quantization of the electronic states, endowing 2DGFs with quantum-confinement-augmented optical nonlinearity, particularly leading to more than two orders of magnitude enhancement in harmonic generation compared with their thick polycrystalline counterparts. The nanometer-scale thickness and single crystal quality makes 2DGFs a promising platform for realizing plasmonic nanostructures with nanoscale optical confinement. This is demonstrated by patterning 2DGFs into nanoribbon arrays, exhibiting strongly confined near infrared plasmonic resonances with high quality factors. The developed 2DGFs provide an emerging platform for nanophotonic research and open up opportunities for applications in ultrathin plasmonic, optoelectronic and quantum devices.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

A Heterostructured Gel Polymer Electrolyte Modified by MoS2 for High-Performance Lithium-Sulfur Batteries.

In Li-S batteries, the shuttle effect of polysulfide lithium (LiPS) on the cathode side and the growth of lithium dendrites on the anode side are two major problems that lead to an insufficient cycle life. Herein, in light of the challenges brought on by the different chemical environments on both sides of Li-S batteries, a heterostructured poly(ethyl acrylate-co-ionic liquid) gel electrolyte with a single-sided electrocatalytic reduced graphene oxide/MoS2 coating (MoS2@rGO-GPE) was developed in order to assemble a high-performance Li-S battery with a self-supporting graphene sulfur cathode. In such a device architecture, there is multiposition suppression of the shuttle effect; that is, the confinement of the graphene foam, the catalysis of the MoS2 composite, and the capture of the gel polymer electrolyte. Our results show that the ionic conductivity of the heterostructured electrolyte is 1.98 mS cm-1, and the Li ion transference number reaches 0.81. The assembled lithium-sulfur battery displays a high initial discharge capacity of 1027 mAh g-1 at 0.1 C, superior cycle stability (80% capacity retention after 500 cycles), and excellent rate performance. This design strategy provides a valuable route for the development of high-performance lithium-sulfur batteries.

Transcriptome sequencing identifies novel EVX fusions involved in transcriptional activation of HOX family genes in pediatric immature T-cell acute lymphoblastic leukemia: two cases reports and a literature review.

Driver genomic alterations in pediatric immature T-cell acute lymphoblastic leukemia are not fully known. We report two cases of novel EVX fusions involved in the transcriptional activation of HOX family genes, ETV6::EVX2 and MSI2::EVX1/HOXA13, which activate HOXD and HOXA cluster genes transcription through enhancer hijacking. HOXA and HOXD were the only key transcription factors activated in these cases, which indicates their important roles in leukemogenesis. Our findings elucidate potential drivers for development of T-cell lymphoblastic leukemia, and are valuable for diagnosis and risk stratification of pediatric T-ALL in the era of precision medicine.

Screen-printed highly stretchable and stable flexible electrodes with a negative Poisson's ratio structure for supercapacitors.

Flexible power sources are crucial to developing flexible electronic systems; nonetheless, the current poor stretchability and stability of flexible power sources hinder their application in such devices. Accordingly, the stretchability and fatigue stability of flexible power sources are crucial for the practical application of flexible electronic systems. In this work, a flexible electrode with an arc-shaped star concave negative Poisson's ratio (NPR) structure is fabricated through the screen printing process. Using the combination of finite element analysis (FEA) and tensile tests, it is proven that the arc-shaped star concave NPR electrode can effectively reduce the maximum tensile stress and increase the maximum elongation (maximum elongation 140%). Furthermore, the flexible electrodes prepared in this study are assembled into all-solid-state symmetric supercapacitors (SSCs), and their electrochemical properties are tested. The SSC prepared in this study has a high areal capacitance of 243.1 mF cm-2. It retains 89.25% of its initial capacity after 5000 times of folding and can maintain a stable output even in extreme deformation, which indicates that the SSC prepared in this study has excellent stability. The SSC with the advantages mentioned above obtained in this study is expected to provide new opportunities to develop flexible electronic systems.

Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia.

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.

Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast.

Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The fission yeast Schizosaccharomyces pombe HP1 family members Chp2 and Swi6 are important for heterochromatin assembly and transcriptional silencing, but their precise roles are not fully understood. Here, we show that Swi6 and Chp2 associate with histone deacetylase (HDAC) protein complexes containing class I HDAC Clr6 and class II HDAC Clr3 (a component of Snf2/HDAC repressor complex), which are critical for transcriptional silencing of centromeric repeats targeted by the heterochromatin machinery. Mapping of RNA polymerase (Pol) II distribution in single and double mutant backgrounds revealed that Swi6 and Chp2 proteins and their associated HDAC complexes have overlapping functions in limiting Pol II occupancy across pericentromeric heterochromatin domains. The purified Swi6 fraction also contains factors involved in various chromosomal processes such as chromatin remodeling and DNA replication. Also, Swi6 copurifies with Mis4 protein, a cohesin loading factor essential for sister chromatid cohesion, and with centromere-specific histone H3 variant CENP-A, which is incorporated into chromatin in a heterochromatin-dependent manner. These analyses suggest that among other functions, HP1 proteins associate with chromatin-modifying factors that in turn cooperate to assemble repressive chromatin; thus, precluding accessibility of underlying DNA sequences to transcriptional machinery.

Increase the Power of Epigenome-Wide Association Testing Using ICC-Based Hypothesis Weighting.

For large-scale hypothesis testing such as epigenome-wide association testing, adaptively focusing power on the more promising hypotheses can lead to a much more powerful multiple testing procedure. In this chapter, we introduce a multiple testing procedure that weights each hypothesis based on the intraclass correlation coefficient (ICC), a measure of "noisiness" of CpG methylation measurement, to increase the power of epigenome-wide association testing. Compared to the traditional multiple testing procedure on a filtered CpG set, the proposed procedure circumvents the difficulty to determine the optimal ICC cutoff value and is overall more powerful. We illustrate the procedure and compare the power to classical multiple testing procedures using an example data.