Sungroh Yoon

Prediction of regulatory modules comprising microRNAs and target genes

MOTIVATION MicroRNAs (miRNAs) are small endogenous RNAs that can play important regulatory roles via the RNA-interference pathway by targeting mRNAs for cleavage or translational repression. We propose a computational method to predict miRNA regulatory modules (MRMs) or groups of miRNAs and target genes that are believed to participate cooperatively in post-transcriptional gene regulation. RESULTS We tested our method with the human genes and miRNAs, predicting 431 MRMs. We analyze a module with genes: BTG2, WT1, PPM1D, PAK7 and RAB9B, and miRNAs: miR-15a and miR-16. Review of the literature and annotation with Gene Ontology terms reveal that the roles of these genes can indeed be closely related in specific biological processes, such as gene regulation involved in breast, renal and prostate cancers. Furthermore, it has been reported that miR-15a and miR-16 are deleted together in certain types of cancer, suggesting a possible connection between these miRNAs and cancers. Given that most known functionalities of miRNAs are related to negative gene regulation, extending our approach and exploiting the insight thus obtained may provide clues to achieving practical accuracy in the reverse-engineering of gene regulatory networks. AVAILABILITY A list of predicted modules is available from the authors upon request.

Got target? Computational methods for microRNA target prediction and their extension.

MicroRNAs (miRNAs) are a class of small RNAs of 19-23 nucleotides that regulate gene expression through target mRNA degradation or translational gene silencing. The miRNAs are reported to be involved in many biological processes, and the discovery of miRNAs has been provided great impacts on computational biology as well as traditional biology. Most miRNA-associated computational methods comprise the prediction of miRNA genes and their targets, and increasing numbers of computational algorithms and web-based resources are being developed to fulfill the need of scientists performing miRNA research. Here we summarize the rules to predict miRNA targets and introduce some computational algorithms that have been developed for miRNA target prediction and the application of the methods. In addition, the issue of target gene validation in an experimental way will be discussed.

Deep learning in bioinformatics

In the era of big data, transformation of biomedical big data into valuable knowledge has been one of the most important challenges in bioinformatics. Deep learning has advanced rapidly since the early 2000s and now demonstrates state-of-the-art performance in various fields. Accordingly, application of deep learning in bioinformatics to gain insight from data has been emphasized in both academia and industry. Here, we review deep learning in bioinformatics, presenting examples of current research. To provide a useful and comprehensive perspective, we categorize research both by the bioinformatics domain (i.e. omics, biomedical imaging, biomedical signal processing) and deep learning architecture (i.e. deep neural networks, convolutional neural networks, recurrent neural networks, emergent architectures) and present brief descriptions of each study. Additionally, we discuss theoretical and practical issues of deep learning in bioinformatics and suggest future research directions. We believe that this review will provide valuable insights and serve as a starting point for researchers to apply deep learning approaches in their bioinformatics studies.

RNA design rules from a massive open laboratory

Significance Self-assembling RNA molecules play critical roles throughout biology and bioengineering. To accelerate progress in RNA design, we present EteRNA, the first internet-scale citizen science “game” scored by high-throughput experiments. A community of 37,000 nonexperts leveraged continuous remote laboratory feedback to learn new design rules that substantially improve the experimental accuracy of RNA structure designs. These rules, distilled by machine learning into a new automated algorithm EteRNABot, also significantly outperform prior algorithms in a gauntlet of independent tests. These results show that an online community can carry out large-scale experiments, hypothesis generation, and algorithm design to create practical advances in empirical science. Self-assembling RNA molecules present compelling substrates for the rational interrogation and control of living systems. However, imperfect in silico models—even at the secondary structure level—hinder the design of new RNAs that function properly when synthesized. Here, we present a unique and potentially general approach to such empirical problems: the Massive Open Laboratory. The EteRNA project connects 37,000 enthusiasts to RNA design puzzles through an online interface. Uniquely, EteRNA participants not only manipulate simulated molecules but also control a remote experimental pipeline for high-throughput RNA synthesis and structure mapping. We show herein that the EteRNA community leveraged dozens of cycles of continuous wet laboratory feedback to learn strategies for solving in vitro RNA design problems on which automated methods fail. The top strategies—including several previously unrecognized negative design rules—were distilled by machine learning into an algorithm, EteRNABot. Over a rigorous 1-y testing phase, both the EteRNA community and EteRNABot significantly outperformed prior algorithms in a dozen RNA secondary structure design tests, including the creation of dendrimer-like structures and scaffolds for small molecule sensors. These results show that an online community can carry out large-scale experiments, hypothesis generation, and algorithm design to create practical advances in empirical science.

Concurrent simulation platform for energy-aware smart metering systems

We propose a simulation framework that can model a house equipped with various home appliances and next-generation smart metering devices. This simulator can predict the power dissipation profiles of individual appliances as well as the cumulative energy consumption of the house in a realistic manner. We utilize SystemC, a concurrent system-modeling methodology originally developed and populated in the design automation community. According to our experiments with various consumer electronics devices, the simulated and measured power profiles match very closely, producing the average correlation of 0.973. The deviation of simulated energy consumption from the measurement was also negligible. Using the proposed simulation platform, any electricity consumer interested in energy saving as well as the designer of a new smart metering system will be able to simulate and test their system from energy perspectives. As a case study, we show how the size of the accumulative power peak of a house can be reduced significantly by using the information provided by the proposed simulator.

Run-Time Adaptive Workload Estimation for Dynamic Voltage Scaling

Dynamic voltage scaling (DVS) is a popular energy-saving technique for real-time tasks. The effectiveness of DVS critically depends on the accuracy of workload estimation, since DVS exploits the slack or the difference between the deadline and execution time. Many existing DVS techniques are profile based and simply utilize the worst-case or average execution time without estimation. Several recent approaches recognize the importance of workload estimation and adopt statistical estimation techniques. However, these approaches still require extensive profiling to extract reliable workload statistics and furthermore cannot effectively handle time-varying workloads. Feedback-control-based adaptive algorithms have been proposed to handle such nonstationary workloads, but their results are often too sensitive to parameter selection. To overcome these limitations of existing approaches, we propose a novel workload estimation technique for DVS. This technique is based on the Kalman filter and can estimate the processing time of workloads in a robust and accurate manner by adaptively calibrating estimation error by feedback. We tested the proposed method with workloads of various characteristics extracted from eight MPEG video clips. To thoroughly evaluate the performance of our approach, we used both a cycle-accurate simulator and an XScale-based test board. Our simulation result demonstrates that the proposed technique outperforms the compared alternatives with respect to the ability to meet given timing and Quality of Service constraints. Furthermore, we found that the accuracy of our approach is almost comparable to the oracle accuracy achievable only by offline analysis. Experimental results indicate that using our approach can reduce energy consumption by 57.5% on average, only with negligible deadline miss ratio (DMR) around 6.1%. Moreover, the average of computational overheads for the proposed technique is just 0.3%, which is the minimum value compared to other methods. More importantly, the DMR of our method is bounded by 11.7% in the worst case, while those of other methods are twice or more than ours.

Discovering Coherent Biclusters from Gene Expression Data Using Zero-Suppressed Binary Decision Diagrams

The biclustering method can be a very useful analysis tool when some genes have multiple functions and experimental conditions are diverse in gene expression measurement. This is because the biclustering approach, in contrast to the conventional clustering techniques, focuses on finding a subset of the genes and a subset of the experimental conditions that together exhibit coherent behavior. However, the biclustering problem is inherently intractable, and it is often computationally costly to find biclusters with high levels of coherence. In this work, we propose a novel biclustering algorithm that exploits the zero-suppressed binary decision diagrams (ZBDDs) data structure to cope with the computational challenges. Our method can find all biclusters that satisfy specific input conditions, and it is scalable to practical gene expression data. We also present experimental results confirming the effectiveness of our approach.

HiTRACE: High-throughput robust analysis for capillary electrophoresis

MOTIVATION Capillary electrophoresis (CE) of nucleic acids is a workhorse technology underlying high-throughput genome analysis and large-scale chemical mapping for nucleic acid structural inference. Despite the wide availability of CE-based instruments, there remain challenges in leveraging their full power for quantitative analysis of RNA and DNA structure, thermodynamics and kinetics. In particular, the slow rate and poor automation of available analysis tools have bottlenecked a new generation of studies involving hundreds of CE profiles per experiment. RESULTS We propose a computational method called high-throughput robust analysis for capillary electrophoresis (HiTRACE) to automate the key tasks in large-scale nucleic acid CE analysis, including the profile alignment that has heretofore been a rate-limiting step in the highest throughput experiments. We illustrate the application of HiTRACE on 13 datasets representing 4 different RNAs, 3 chemical modification strategies and up to 480 single mutant variants; the largest datasets each include 87 360 bands. By applying a series of robust dynamic programming algorithms, HiTRACE outperforms prior tools in terms of alignment and fitting quality, as assessed by measures including the correlation between quantified band intensities between replicate datasets. Furthermore, while the smallest of these datasets required 7-10 h of manual intervention using prior approaches, HiTRACE quantitation of even the largest datasets herein was achieved in 3-12 min. The HiTRACE method, therefore, resolves a critical barrier to the efficient and accurate analysis of nucleic acid structure in experiments involving tens of thousands of electrophoretic bands.

Deduplication in SSDs: Model and quantitative analysis

In NAND Flash-based SSDs, deduplication can provide an effective resolution of three critical issues: cell lifetime, write performance, and garbage collection overhead. However, deduplication at SSD device level distinguishes itself from the one at enterprise storage systems in many aspects, whose success lies in proper exploitation of underlying very limited hardware resources and workload characteristics of SSDs. In this paper, we develop a novel deduplication framework elaborately tailored for SSDs. We first mathematically develop an analytical model that enables us to calculate the minimum required duplication rate in order to achieve performance gain given deduplication overhead. Then, we explore a number of design choices for implementing deduplication components by hardware or software. As a result, we propose two acceleration techniques: sampling-based filtering and recency-based fingerprint management. The former selectively applies deduplication based upon sampling and the latter effectively exploits limited controller memory while maximizing the deduplication ratio. We prototype the proposed deduplication framework in three physical hardware platforms and investigate deduplication efficiency according to various CPU capabilities and hardware/software alternatives. Experimental results have shown that we achieve the duplication rate ranging from 4% to 51%, with an average of 17%, for the nine workloads considered in this work. The response time of a write request can be improved by up to 48% with an average of 15%, while the lifespan of SSDs is expected to increase up to 4.1 times with an average of 2.4 times.

Standardization of RNA Chemical Mapping Experiments

Chemical mapping experiments offer powerful information about RNA structure but currently involve ad hoc assumptions in data processing. We show that simple dilutions, referencing standards (GAGUA hairpins), and HiTRACE/MAPseeker analysis allow rigorous overmodification correction, background subtraction, and normalization for electrophoretic data and a ligation bias correction needed for accurate deep sequencing data. Comparisons across six noncoding RNAs stringently test the proposed standardization of dimethyl sulfate (DMS), 2′-OH acylation (SHAPE), and carbodiimide measurements. Identification of new signatures for extrahelical bulges and DMS “hot spot” pockets (including tRNA A58, methylated in vivo) illustrates the utility and necessity of standardization for quantitative RNA mapping.