High-Performance Plasma Biomarker Panel for Alzheimer's Disease Screening Using a Femtomolar-Level Label-Free Biosensing System.

Alzheimer's disease (AD) is the most common cause of dementia in older people. However, diagnosing AD through noncognitive methods, such as invasive cerebrospinal fluid sampling or radioactive positron emission tomography, has limited applications. Herein, the femtomolar levels of AD biomarkers amyloid ß 40 (Aß40), amyloid ß 42 (Aß42), phosphorylated tau 181 (P-tau181), phosphorylated tau 217 (P-tau217), and neurofilament light chain (NfL) were determined in human plasma in multicenter clinical cohorts using an ultrasensitive graphene field-effect transistor sensor. A machine-learning algorithm was also used to assemble these plasma biomarkers and optimize their performance in discriminating individual stages of Alzheimer's dementia progression. The "composite-info" biomarker panel, which combines these biomarkers and clinical information, considerably improved the staging performance in AD progression. It achieved an area under the curve of >0.94 in the receiver operator characteristic (ROC) curve. In addition, the panel demonstrated an advantage in the individual-based stage assessment compared with that of the Mini-Mental State Examination/Montreal Cognitive Assessment and nuclear magnetic resonance imaging. This study provides a composite biomarker panel for the screening and early diagnosis of AD using a rapid detection system.

Route to Cost-Effective Fabrication of Wafer-Scale Nanostructure through Self-Priming Nanoimprint.

Nanoimprint technology is powerful for fabricating nanostructures in a large area. However, expensive equipment, high cost, and complex process conditions hinder the application of nano-imprinting technology. Therefore, double-layer self-priming nanoimprint technology was proposed to fabricate ordered metal nanostructures uniformly on 4-inch soft and hard substrates without the aid of expensive instruments. Different nanostructure (gratings, nanoholes and nanoparticles) and different materials (metal and MoS2) were patterned, which shows wide application of double-layer self-priming nanoimprint technology. Moreover, by a double-layer system, the width and the height of metal can be adjusted through the photoresist thickness and developing condition, which provide a programmable way to fabricate different nanostructures using a single mold. The double-layer self-priming nanoimprint method can be applied in poor condition without equipment and be programmable in nanostructure parameters using a single mold, which reduces the cost of instruments and molds.

Enhanced-fluorescent imaging and targeted therapy of liver cancer using highly luminescent carbon dots-conjugated foliate.

Carbon dots (CDs) have shown great potential in drug delivery and biological imaging applications. In this work, a doxorubicin (DOX) delivery carrier and imaging probe for liver cancer-targeted therapy was designed based on CDs with high fluorescence quantum yield (97%), aiming to enhance the antitumor activity and imaging efficiency. Folic acid (FA), which showed high expression in hepatoma cells, was used as targeting components to modify CDs (FA-CDs), and then FA-CDs-DOX was obtained by loading DOX. Results show that CDs and FA-CDs have good biocompatibility, and the DOX release from FA-CDs-DOX is targeted and selective. Confocal microscope demonstrates that FA-CDs-DOX has excellent ability of fluorescence imaging in liver cancer cells. The imaging in vivo shows the fluorescence intensity of FA-CDs-DOX is strong enough to penetrate tumor tissue and skin, further verifying its enhanced-fluorescent imaging effects. Tumor inhibition in vivo indicates that the targeting ability of FA-CDs-DOX is significantly higher than that of free DOX, showing obvious better therapeutic effect. To sum up, the targeted and fluorescent drug delivery system based on CDs with high fluorescence quantum yield show an excellent imaging in vivo and tumor inhibition effect, which provide a novel strategy for promoting the potential clinical application of CDs in liver cancer treatment.

Smartphone Biosensor System with Multi-Testing Unit Based on Localized Surface Plasmon Resonance Integrated with Microfluidics Chip.

Detecting biomarkers is an efficient method to diagnose and monitor patients' stages. For more accurate diagnoses, continuously detecting and monitoring multiple biomarkers are needed. To achieve point-of-care testing (POCT) of multiple biomarkers, a smartphone biosensor system with the multi-testing-unit (SBSM) based on localized surface plasmon resonance (LSPR) integrated multi-channel microfluidics was presented. The SBSM could simultaneously record nine sensor units to achieve the detection of multiple biomarkers. Additional 72 sensor units were fabricated for further verification. Well-designed modularized attachments consist of a light source, lenses, a grating, a case, and a smartphone shell. The attachments can be well assembled and attached to a smartphone. The sensitivity of the SBSM was 161.0 nm/RIU, and the limit of detection (LoD) reached 4.2 U/mL for CA125 and 0.87 U/mL for CA15-3 through several clinical serum specimens testing on the SBSM. The testing results indicated that the SBSM was a useful tool for detecting multi-biomarkers. Comparing with the enzyme-linked immunosorbent assays (ELISA) results, the results from the SBSM were correlated and reliable. Meanwhile, the SBSM was convenient to operate without much professional skill. Therefore, the SBSM could become useful equipment for point-of-care testing due to its small size, multi-testing unit, usability, and customizable design.

Label-Free Exosome Detection Based on a Low-Cost Plasmonic Biosensor Array Integrated with Microfluidics.

Localized surface plasmon resonance-based plasmonic biosensors are interesting candidates for the design of portable optical biosensor platforms owing to their integration, miniaturization, multiparameter, real-time, and label-free detection characteristics. Plasmonic biosensor arrays that have been combined with microfluidics have been developed herein to detect exosomes label-free. Gold nano-ellipsoid arrays were fabricated with low-cost anodic aluminum oxide thin films that act as shadow masks for evaporation of Au. The nano-ellipsoid arrays were integrated with a microfluidic chip to achieve multiparameter detection. The anti-CD63 antibody that is specific to the exosome transmembrane protein CD63 is modified on the surface of the nano-ellipsoids. Exosome samples were injected into the biosensor platform at different concentrations and detected successfully. The detection limit was 1 ng/mL. The proposed plasmonic biosensor array can be universally applicable for the detection of other biomarkers by simply changing the antibody on the surface of the Au nano-ellipsoids. Moreover, this biosensor platform is envisaged to be potentially useful in the development of low-cost plasmonic-based biosensors for biomarker detection and for the investigation of exosomes for noninvasive disease diagnoses.

Exploring surface sensitivity of Rayleigh anomaly in metal/dielectric multilayer gratings.

Biosensors based on Rayleigh anomaly (RA) in metal gratings exhibit impressive bulk refractive index (RI) sensitivity and narrow linewidth. However, the electric field enhancement extends far away from surface of the gratings, which limits the application on biosensor where the RI changes are restricted at the sensor interface. To overcome this shortcoming, a novel grating composed of a 8-layer Au/Al2O3 stack was optimized by numerical simulation. The electric field is limited in several hundreds of nanometers from surface. The surface sensitivity increases 10 times than that of Au gratings at the detection depth of less than 400 nm. The surface index sensitivity can be improved 5 times under oblique incidence than that under normal incidence when the thickness of cover media is 20 nm.

Piezoelectric Microchip for Cell Lysis through Cell-Microparticle Collision within a Microdroplet Driven by Surface Acoustic Wave Oscillation.

Cell lysis is an important and crucial step for the detection of intracellular secrets. Usually, cell lysis is based on strong ultrasonic waves or toxic chemical regents, which require a large amount of cell suspension. To obtain high efficiency cell lysis for a small amount of sample, a mechanical cell lysis method based on a surface acoustic wave (SAW) microchip is proposed. The microchip simply consists of a piece of LiNbO3 crystal substrate, interdigitated transducers (IDTs) with 80 pairs of parallel electrodes and 3M Magic Tapes. The modulated input electrical signal is coupled into the substrate through IDTs, which produces an acoustic stream in the droplet on the surface of a substrate. When a biofluid droplet containing cells and microparticles is dropped on the surface of the microchip, the cells and microparticles are accelerated and collide with each other. The fluorescence staining results illustrate that the cell membrane is efficiently destroyed and that proteins as well as nucleic acids inside the cell are released. The experimental results show that this method has a high efficiency and low sample consumption. The potential application is the pretreatment of a small amount of tested sample in a hospital or biolab.

COSMIC: the Catalogue Of Somatic Mutations In Cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC's deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.

A PDMS Device Coupled with Culture Dish for In Vitro Cell Migration Assay.

Cell migration and invasion are important factors during tumor progression and metastasis. Wound-healing assay and the Boyden chamber assay are efficient tools to investigate tumor development because both of them could be applied to measure cell migration rate. Therefore, a simple and integrated polydimethylsiloxane (PDMS) device was developed for cell migration assay, which could perform quantitative evaluation of cell migration behaviors, especially for the wound-healing assay. The integrated device was composed of three units, which included cell culture dish, PDMS chamber, and wound generation mold. The PDMS chamber was integrated with cell culture chamber and could perform six experiments under different conditions of stimuli simultaneously. To verify the function of this device, it was utilized to explore the tumor cell migration behaviors under different concentrations of fetal bovine serum (FBS) and transforming growth factor (TGF-ß) at different time points. This device has the unique capability to create the "wound" area in parallel during cell migration assay and provides a simple and efficient platform for investigating cell migration assay in biomedical application.

Coordination ability determined transition metal ions substitution of Tb in Tb-Asp fluorescent nanocrystals and a facile ions-detection approach.

Although the synthesis and fluorescent properties of lanthanide-amino acid complex nanostructures have been investigated extensively, limited studies have been reported on metal ions' substitution ability for the lanthanide ions in the complex and their effect on the fluorescent property. In this study, taking biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the substitution mechanism of metal ions, particularly transition metals, for Tb ions in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp nanocrystals after substitution were systematically investigated. The experimental results illustrated that metal ions with higher electronegativity, higher valence, and smaller radius possess stronger ability for Tb ions' substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions' concentration on the fluorescent property of Tb-Asp, a facile method for copper ions detection with high sensitivity was proposed by measuring the fluorescent intensity of Tb-Asp nanocrystals' suspensions containing different concentrations of copper ions. The good biocompatibility, great convenience of synthesis and sensitive detection ability make Tb-Asp nanocrystals a very low cost and effective material for metal ions detection, which also opens a new door for practical applications of metal-Asp coordinated nanocrystals.

Polylactic Acid Nanopillar Array-Driven Osteogenic Differentiation of Human Adipose-Derived Stem Cells Determined by Pillar Diameter.

Numerous studies have determined that physical cues, especially the nanotopography of materials, play key roles in directing stem cell differentiation. However, most research on nanoarrays for stem cell fate regulation is based on nonbiodegradable materials, such as silicon wafers, TiO2, and poly(methyl methacrylate), which are rarely used as tissue engineering biomaterials. In this study, we prepared biodegradable polylactic acid (PLA) nanopillar arrays with different diameters but the same center-to-center distance using a series of anodic aluminum oxide nanowell arrays as templates. Human adipose-derived stem cells (hADSCs) were selected to investigate the effect of the diameter of PLA nanopillar arrays on stem cell differentiation. By culturing hADSCs without the assistance of any growth factors or osteogenic-induced media, the differentiation tendencies of hADSCs on the nanopillar arrays were assessed at the gene and protein levels. The assessment results suggested that the osteogenic differentiation of hADSCs can be driven by nanopillar arrays, especially by nanopillar arrays with a diameter of 200 nm. Moreover, an in vivo animal model of the samples demonstrated that PLA film with the 200 nm pillar array exhibits an improved ectopic osteogenic ability compared with the planar PLA film after 4 weeks of ectopic implantation. This study has provided a new variable to investigate in the interaction between stem cells and nanoarray structures, which will guide the bone regeneration clinical research field. This work paves the way for the utility of degradable biopolymer nanoarrays with specific geometrical and mechanical signals in biomedical applications, such as patches and strips for spine fusion, bone crack repair, and restoration of tooth enamel.

Hydroxyapatite nanobelt/polylactic acid Janus membrane with osteoinduction/barrier dual functions for precise bone defect repair.

Controllable osteoinduction maintained in the original defect area is the key to precise bone repair. To meet the requirement of precise bone regeneration, a hydroxyapatite (HAp) nanobelt/polylactic acid (PLA) (HAp/PLA) Janus membrane has been successfully prepared in this study by coating PLA on a paper-like HAp nanobelt film by a casting-pervaporation method. The Janus membrane possesses dual functions: excellent osteoinduction from the hydrophilic HAp nanobelt side and barrier function originating from the hydrophobic PLA film. The cell viability and osteogenic differentiation ability of human adipose-derived stem cells (hADSCs) on the Janus membrane were assessed. The in vitro experimental results prove that the HAp nanobelt side presents high cell viability and efficient osteoinduction without any growth factor and that the PLA side can prohibit cell attachment. The in vivo repair experiments on a rat mandible defect model prove that the PLA side can prevent postoperative adhesion between bone and adjacent soft tissues. Most importantly, the HAp side has a strong ability to promote defect repair and bone regeneration. Therefore, the HAp/PLA Janus membrane will have wide applications as a kind of tissue engineering material in precise bone repair because of its unique dual osteoinduction/barrier functions, biocompatibility, low cost, and its ability to be mass-produced. STATE OF SIGNIFICANCE: Precise bone defect repair to keeping tissue integrity and original outline shape is a very important issue for tissue engineering. Here, we have designed and prepared a novel HAp/PLA Janus membrane using a casting-pervaporation method to form a layer of PLA film on paper-like HAp nanobelt film. HAp nanobelt side of the Janus membrane can successfully promote osteogenic differentiation. PLA side of the Janus membrane exhibits good properties as a barrier for preventing the adhesion of cells in vitro. Mandible repair experiments in vivo have shown that the HAp/PLA Janus membrane can promote rat mandible repair on the HAp side and can successfully prevent postoperative adhesion on the PLA side at the same time. Therefore, the HAp/PLA Janus membrane with its osteoinduction/barrier dual functions can be applied to repair bone defect precisely.

Hydrophilic cobalt sulfide nanosheets as a bifunctional catalyst for oxygen and hydrogen evolution in electrolysis of alkaline aqueous solution.

Hydrophilic medium and precursors were used to synthesize a hydrophilic electro-catalyst for overall water splitting. The cobalt sulfide (Co3S4) catalyst exhibits a layered nanosheet structure with a hydrophilic surface, which can facilitate the diffusion of aqueous substrates into the electrode pores and towards the active sites. The Co3S4 catalyst shows excellent bifunctional catalytic activity for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline solution. The assembled water electrolyzer based on Co3S4 exhibits better performance and stability than that of Pt/C-RuO2 catalyst. Thereforce the hydrophilic Co3S4 is a highly promising bifunctional catalyst for the overall water splitting reaction.

One-Dimensional Hydroxyapatite Nanostructures with Tunable Length for Efficient Stem Cell Differentiation Regulation.

It is well-accepted that most osteogenic differentiation processes do need growth factors assistance to improve efficiency. As a material cue, hydroxyapatite (HAp) can promote osteogenic differentiation of stem cells only in a way. Up to now, rare work related to the relationship between HAp nanostructures and stem cells in osteogenic differentiation process without the assistance of growth factors has been reported. In this study, one-dimensional (1D) HAp nanostructures with tunable length were synthesized by an oleic acid assisted solvothermal method by adjusting the alcohol/water ratio (η). The morphology of 1D HAp nanostructures can be changed from long nanowires into nanorods with the η value change. Different substrates constructed by 1D HAp nanostructures were prepared to investigate the effect of morphology of nanostructured HAp on stem cell fate without any growth factors or differentiation induce media. Human adipose-derived stem cells (hADSCs), a kind of promising stem cell for autologous stem cell tissue engineering, were used as the stem cell model. The experiments prove that HAp morphology can determine the performance of hADSCs cultured on different substrates. Substrate constructed by HAp nanorods (100 nm) is of little benefit to osteogenic differentiations. Substrate constructed on HAp long nanowires (50 µm) causes growth and spread inhibition of hADSCs, which even causes most cells death after 7 days of culture. However, substrate constructed by HAp short nanowires (5 µm) can destine the hADSCs differentiation to osteoblasts efficiently in normal medium (after 3 weeks) without any growth factors. It is surprise that hADSCs have changed to polyhedral morphology and exhibited the tendency to osteogenic differentiation after only 24 h culture. Hydroxyapatite nanostructures mediated stem cell osteogenic differentiation excluding growth factors provides a powerful cue to design biomaterials with special nanostructures, and helps to elucidate the interaction of stem cell and biomaterials nanostructures. The results from this study are promising for application in bone tissue engineering.

An integrated method for cell isolation and migration on a chip.

Tumour cell migration has an important impact on tumour metastasis. Magnetic manipulation is an ascendant method for guiding and patterning cells. Here, a unique miniaturized microfluidic chip integrating cell isolation and migration assay was designed to isolate and investigate cell migration. The chip was fabricated and composed of a magnet adapter, a polytetrafluoroethylene(PDMS) microfluidic chip and six magnetic rings. This device was used to isolate MCF-7 cells from MDA-MB-231-RFP cells and evaluate the effects of TGF-ß on MCF-7 cells. First, the two cell types were mixed and incubated with magnetic beads modified with an anti-EpCAM antibody. Then, they were slowly introduced into the chip. MCF-7 cells bond to the magnetic beads in a ring-shaped pattern, while MDA-MB-231-RFP cells were washed away by PBS. Cell viability was examined during culturing in the micro-channel. The effects of TGF-ß on MCF-7 cells were evaluated by migration distance and protein expression. The integrated method presented here is novel, low-cost and easy for performing cell isolation and migration assay. The method could be beneficial for developing microfluidic device applications for cancer metastasis research and could provide a new method for biological experimentation.

Terbium-Aspartic Acid Nanocrystals with Chirality-Dependent Tunable Fluorescent Properties.

Terbium-aspartic acid (Tb-Asp) nanocrystals with chirality-dependent tunable fluorescent properties can be synthesized through a facile synthesis method through the coordination between Tb and Asp. Asp with different chirality (dextrorotation/d and levogyration/l) changes the stability of the coordination center following fluorescent absorption/emission ability differences. Compared with l-Asp, d-Asp can coordinate Tb to form a more stable center, following the higher quantum yield and longer fluorescence life. Fluorescence intensity of Tb-Asp linearly increases with increase ratio of d-Asp in the mixed chirality Tb-Asp system, and the fluorescent properties of Tb-Asp nanocrystals can be tuned by adjusting the chirality ratio. Tb-Asp nanocrystals possess many advantage, such as high biocompatibility, without any color in visible light irradiation, monodispersion with very small size, and long fluorescent life. Those characteristics will give them great potential in many application fields, such as low-cost antifake markers and advertisements using inkjet printers or for molds when dispersed in polydimethylsiloxane. In addition, europium can also be used to synthesize Eu-Asp nanoparticles. Importantly, the facile, low-cost, high-yield, mass-productive "green" process provides enormous advantages for synthesis and application of fluorescent nanocrystals, which will have great impact in nanomaterial technology.

Prolonged fluorescence lifetime of carbon quantum dots by combining with hydroxyapatite nanorods for bio-applications.

Carbon quantum dots (CQDs) are a new type of fluorescent nanoparticle for cell imaging and tracking. However, they would easily diffuse and quench, followed by the loss of their fluorescence ability. By connecting their functional groups with other nanoparticles, the CQDs will be protected from destruction and exhibit long-time fluorescence. Here, carbon quantum dot-hydroxyapatite (CQD-HAp) hybrid nanorods were prepared by the self-assembly of CQDs on the surface of HAp nanorods through a facile one-pot process. The morphology and size of the CQD-HAp hybrid nanorods can be well controlled by using oleic acid, which meanwhile is the source of CQDs. The hydrophilic CQD-HAp hybrid nanorods have prolonged fluorescence life due to the connection between CQDs and HAp nanorods, and exhibit a higher fluorescence quantum yield than pure CQDs. In addition, when hybrid nanorods load doxorubicin (Dox) to form Dox-CQD-HAp hybrid nanorods, they can more efficiently kill human cervical cancer (HeLa) cells, rather than human prostatic cancer (PC-3) cells. Long time fluorescence for cell imaging and high efficiency in killing cancer cells as a drug-delivery medium make CQD-HAp hybrid nanorods have great potential applications in the bio-field.

CGDM: collaborative genomic data model for molecular profiling data using NoSQL.

MOTIVATION: High-throughput molecular profiling has greatly improved patient stratification and mechanistic understanding of diseases. With the increasing amount of data used in translational medicine studies in recent years, there is a need to improve the performance of data warehouses in terms of data retrieval and statistical processing. Both relational and Key Value models have been used for managing molecular profiling data. Key Value models such as SeqWare have been shown to be particularly advantageous in terms of query processing speed for large datasets. However, more improvement can be achieved, particularly through better indexing techniques of the Key Value models, taking advantage of the types of queries which are specific for the high-throughput molecular profiling data. RESULTS: In this article, we introduce a Collaborative Genomic Data Model (CGDM), aimed at significantly increasing the query processing speed for the main classes of queries on genomic databases. CGDM creates three Collaborative Global Clustering Index Tables (CGCITs) to solve the velocity and variety issues at the cost of limited extra volume. Several benchmarking experiments were carried out, comparing CGDM implemented on HBase to the traditional SQL data model (TDM) implemented on both HBase and MySQL Cluster, using large publicly available molecular profiling datasets taken from NCBI and HapMap. In the microarray case, CGDM on HBase performed up to 246 times faster than TDM on HBase and 7 times faster than TDM on MySQL Cluster. In single nucleotide polymorphism case, CGDM on HBase outperformed TDM on HBase by up to 351 times and TDM on MySQL Cluster by up to 9 times. AVAILABILITY AND IMPLEMENTATION: The CGDM source code is available at https://github.com/evanswang/CGDM. CONTACT: y.guo@imperial.ac.uk.

High dimensional biological data retrieval optimization with NoSQL technology.

BACKGROUND: High-throughput transcriptomic data generated by microarray experiments is the most abundant and frequently stored kind of data currently used in translational medicine studies. Although microarray data is supported in data warehouses such as tranSMART, when querying relational databases for hundreds of different patient gene expression records queries are slow due to poor performance. Non-relational data models, such as the key-value model implemented in NoSQL databases, hold promise to be more performant solutions. Our motivation is to improve the performance of the tranSMART data warehouse with a view to supporting Next Generation Sequencing data. RESULTS: In this paper we introduce a new data model better suited for high-dimensional data storage and querying, optimized for database scalability and performance. We have designed a key-value pair data model to support faster queries over large-scale microarray data and implemented the model using HBase, an implementation of Google's BigTable storage system. An experimental performance comparison was carried out against the traditional relational data model implemented in both MySQL Cluster and MongoDB, using a large publicly available transcriptomic data set taken from NCBI GEO concerning Multiple Myeloma. Our new key-value data model implemented on HBase exhibits an average 5.24-fold increase in high-dimensional biological data query performance compared to the relational model implemented on MySQL Cluster, and an average 6.47-fold increase on query performance on MongoDB. CONCLUSIONS: The performance evaluation found that the new key-value data model, in particular its implementation in HBase, outperforms the relational model currently implemented in tranSMART. We propose that NoSQL technology holds great promise for large-scale data management, in particular for high-dimensional biological data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new data model as a basis for migrating tranSMART's implementation to a more scalable solution for Big Data.

Optimising parallel R correlation matrix calculations on gene expression data using MapReduce.

BACKGROUND: High-throughput molecular profiling data has been used to improve clinical decision making by stratifying subjects based on their molecular profiles. Unsupervised clustering algorithms can be used for stratification purposes. However, the current speed of the clustering algorithms cannot meet the requirement of large-scale molecular data due to poor performance of the correlation matrix calculation. With high-throughput sequencing technologies promising to produce even larger datasets per subject, we expect the performance of the state-of-the-art statistical algorithms to be further impacted unless efforts towards optimisation are carried out. MapReduce is a widely used high performance parallel framework that can solve the problem. RESULTS: In this paper, we evaluate the current parallel modes for correlation calculation methods and introduce an efficient data distribution and parallel calculation algorithm based on MapReduce to optimise the correlation calculation. We studied the performance of our algorithm using two gene expression benchmarks. In the micro-benchmark, our implementation using MapReduce, based on the R package RHIPE, demonstrates a 3.26-5.83 fold increase compared to the default Snowfall and 1.56-1.64 fold increase compared to the basic RHIPE in the Euclidean, Pearson and Spearman correlations. Though vanilla R and the optimised Snowfall outperforms our optimised RHIPE in the micro-benchmark, they do not scale well with the macro-benchmark. In the macro-benchmark the optimised RHIPE performs 2.03-16.56 times faster than vanilla R. Benefiting from the 3.30-5.13 times faster data preparation, the optimised RHIPE performs 1.22-1.71 times faster than the optimised Snowfall. Both the optimised RHIPE and the optimised Snowfall successfully performs the Kendall correlation with TCGA dataset within 7 hours. Both of them conduct more than 30 times faster than the estimated vanilla R. CONCLUSIONS: The performance evaluation found that the new MapReduce algorithm and its implementation in RHIPE outperforms vanilla R and the conventional parallel algorithms implemented in R Snowfall. We propose that MapReduce framework holds great promise for large molecular data analysis, in particular for high-dimensional genomic data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new algorithm as a basis for optimising high-throughput molecular data correlation calculation for Big Data.