Lateral Orbitofrontal Cortex Encodes Presence of Risk and Subjective Risk Preference During Decision-Making.

Adaptive decision-making requires consideration of objective risks and rewards associated with each option, as well as subjective preference for risky/safe alternatives. Inaccurate risk/reward estimations can engender excessive risk-taking, a central trait in many psychiatric disorders. The lateral orbitofrontal cortex (lOFC) has been linked to many disorders associated with excessively risky behavior and is ideally situated to mediate risky decision-making. Here, we used single-unit electrophysiology to measure neuronal activity from lOFC of freely moving rats performing in a punishment-based risky decision-making task. Subjects chose between a small, safe reward and a large reward associated with either 0% or 50% risk of concurrent punishment. lOFC activity repeatedly encoded current risk in the environment throughout the decision-making sequence, signaling risk before, during, and after a choice. In addition, lOFC encoded reward magnitude, although this information was only evident during action selection. A Random Forest classifier successfully used neural data accurately to predict the risk of punishment in any given trial, and the ability to predict choice via lOFC activity differentiated between and risk-preferring and risk-averse rats. Finally, risk preferring subjects demonstrated reduced lOFC encoding of risk and increased encoding of reward magnitude. These findings suggest lOFC may serve as a central decision-making hub in which external, environmental information converges with internal, subjective information to guide decision-making in the face of punishment risk.

Unraveling Spatial-Spectral Dynamics of Speech Categorization Speed Using Convolutional Neural Networks.

The process of categorizing sounds into distinct phonetic categories is known as categorical perception (CP). Response times (RTs) provide a measure of perceptual difficulty during labeling decisions (i.e., categorization). The RT is quasi-stochastic in nature due to individuality and variations in perceptual tasks. To identify the source of RT variation in CP, we have built models to decode the brain regions and frequency bands driving fast, medium and slow response decision speeds. In particular, we implemented a parameter optimized convolutional neural network (CNN) to classify listeners' behavioral RTs from their neural EEG data. We adopted visual interpretation of model response using Guided-GradCAM to identify spatial-spectral correlates of RT. Our framework includes (but is not limited to): (i) a data augmentation technique designed to reduce noise and control the overall variance of EEG dataset; (ii) bandpower topomaps to learn the spatial-spectral representation using CNN; (iii) large-scale Bayesian hyper-parameter optimization to find best performing CNN model; (iv) ANOVA and posthoc analysis on Guided-GradCAM activation values to measure the effect of neural regions and frequency bands on behavioral responses. Using this framework, we observe that α-ß (10-20 Hz) activity over left frontal, right prefrontal/frontal, and right cerebellar regions are correlated with RT variation. Our results indicate that attention, template matching, temporal prediction of acoustics, motor control, and decision uncertainty are the most probable factors in RT variation.

Imputation of missing values for electronic health record laboratory data.

Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients' comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method.

Interpretable and parameter optimized ensemble model for knee osteoarthritis assessment using radiographs.

Knee osteoarthritis (KOA) is an orthopedic disorder with a substantial impact on mobility and quality of life. An accurate assessment of the KOA levels is imperative in prioritizing meaningful patient care. Quantifying osteoarthritis features such as osteophytes and joint space narrowing (JSN) from low-resolution images (i.e., X-ray images) are mostly subjective. We implement an objective assessment and quantification of KOA to aid practitioners. In particular, we developed an interpretable ensemble of convolutional neural network (CNN) models consisting of three modules. First, we developed a scale-invariant and aspect ratio preserving model to localize Knee joints. Second, we created multiple instances of "hyperparameter optimized" CNN models with diversity and build an ensemble scoring system to assess the severity of KOA according to the Kellgren-Lawrence grading (KL) scale. Third, we provided visual explanations of the predictions by the ensemble model. We tested our models using a collection of 37,996 Knee joints from the Osteoarthritis Initiative (OAI) dataset. Our results show a superior (13-27%) performance improvement compared to the state-of-the-art methods.

Data-driven machine learning models for decoding speech categorization from evoked brain responses.

Objective.Categorical perception (CP) of audio is critical to understand how the human brain perceives speech sounds despite widespread variability in acoustic properties. Here, we investigated the spatiotemporal characteristics of auditory neural activity that reflects CP for speech (i.e. differentiates phonetic prototypes from ambiguous speech sounds).Approach.We recorded 64-channel electroencephalograms as listeners rapidly classified vowel sounds along an acoustic-phonetic continuum. We used support vector machine classifiers and stability selection to determine when and where in the brain CP was best decoded across space and time via source-level analysis of the event-related potentials.Main results. We found that early (120 ms) whole-brain data decoded speech categories (i.e. prototypical vs. ambiguous tokens) with 95.16% accuracy (area under the curve 95.14%;F1-score 95.00%). Separate analyses on left hemisphere (LH) and right hemisphere (RH) responses showed that LH decoding was more accurate and earlier than RH (89.03% vs. 86.45% accuracy; 140 ms vs. 200 ms). Stability (feature) selection identified 13 regions of interest (ROIs) out of 68 brain regions [including auditory cortex, supramarginal gyrus, and inferior frontal gyrus (IFG)] that showed categorical representation during stimulus encoding (0-260 ms). In contrast, 15 ROIs (including fronto-parietal regions, IFG, motor cortex) were necessary to describe later decision stages (later 300-800 ms) of categorization but these areas were highly associated with the strength of listeners' categorical hearing (i.e. slope of behavioral identification functions).Significance.Our data-driven multivariate models demonstrate that abstract categories emerge surprisingly early (∼120 ms) in the time course of speech processing and are dominated by engagement of a relatively compact fronto-temporal-parietal brain network.

Speech categorization is better described by induced rather than evoked neural activity.

Categorical perception (CP) describes how the human brain categorizes speech despite inherent acoustic variability. We examined neural correlates of CP in both evoked and induced electroencephalogram (EEG) activity to evaluate which mode best describes the process of speech categorization. Listeners labeled sounds from a vowel gradient while we recorded their EEGs. Using a source reconstructed EEG, we used band-specific evoked and induced neural activity to build parameter optimized support vector machine models to assess how well listeners' speech categorization could be decoded via whole-brain and hemisphere-specific responses. We found whole-brain evoked ß-band activity decoded prototypical from ambiguous speech sounds with ∼70% accuracy. However, induced γ-band oscillations showed better decoding of speech categories with ∼95% accuracy compared to evoked ß-band activity (∼70% accuracy). Induced high frequency (γ-band) oscillations dominated CP decoding in the left hemisphere, whereas lower frequencies (θ-band) dominated the decoding in the right hemisphere. Moreover, feature selection identified 14 brain regions carrying induced activity and 22 regions of evoked activity that were most salient in describing category-level speech representations. Among the areas and neural regimes explored, induced γ-band modulations were most strongly associated with listeners' behavioral CP. The data suggest that the category-level organization of speech is dominated by relatively high frequency induced brain rhythms.

Decoding Hearing-Related Changes in Older Adults' Spatiotemporal Neural Processing of Speech Using Machine Learning.

Speech perception in noisy environments depends on complex interactions between sensory and cognitive systems. In older adults, such interactions may be affected, especially in those individuals who have more severe age-related hearing loss. Using a data-driven approach, we assessed the temporal (when in time) and spatial (where in the brain) characteristics of cortical speech-evoked responses that distinguish older adults with or without mild hearing loss. We performed source analyses to estimate cortical surface signals from the EEG recordings during a phoneme discrimination task conducted under clear and noise-degraded conditions. We computed source-level ERPs (i.e., mean activation within each ROI) from each of the 68 ROIs of the Desikan-Killiany (DK) atlas, averaged over a randomly chosen 100 trials without replacement to form feature vectors. We adopted a multivariate feature selection method called stability selection and control to choose features that are consistent over a range of model parameters. We use parameter optimized support vector machine (SVM) as a classifiers to investigate the time course and brain regions that segregate groups and speech clarity. For clear speech perception, whole-brain data revealed a classification accuracy of 81.50% [area under the curve (AUC) 80.73%; F1-score 82.00%], distinguishing groups within ∼60 ms after speech onset (i.e., as early as the P1 wave). We observed lower accuracy of 78.12% [AUC 77.64%; F1-score 78.00%] and delayed classification performance when speech was embedded in noise, with group segregation at 80 ms. Separate analysis using left (LH) and right hemisphere (RH) regions showed that LH speech activity was better at distinguishing hearing groups than activity measured in the RH. Moreover, stability selection analysis identified 12 brain regions (among 1428 total spatiotemporal features from 68 regions) where source activity segregated groups with >80% accuracy (clear speech); whereas 16 regions were critical for noise-degraded speech to achieve a comparable level of group segregation (78.7% accuracy). Our results identify critical time-courses and brain regions that distinguish mild hearing loss from normal hearing in older adults and confirm a larger number of active areas, particularly in RH, when processing noise-degraded speech information.

Increasing the Density of Laboratory Measures for Machine Learning Applications.

BACKGROUND: The imputation of missingness is a key step in Electronic Health Records (EHR) mining, as it can significantly affect the conclusions derived from the downstream analysis in translational medicine. The missingness of laboratory values in EHR is not at random, yet imputation techniques tend to disregard this key distinction. Consequently, the development of an adaptive imputation strategy designed specifically for EHR is an important step in improving the data imbalance and enhancing the predictive power of modeling tools for healthcare applications. METHOD: We analyzed the laboratory measures derived from Geisinger's EHR on patients in three distinct cohorts-patients tested for Clostridioides difficile (Cdiff) infection, patients with a diagnosis of inflammatory bowel disease (IBD), and patients with a diagnosis of hip or knee osteoarthritis (OA). We extracted Logical Observation Identifiers Names and Codes (LOINC) from which we excluded those with 75% or more missingness. The comorbidities, primary or secondary diagnosis, as well as active problem lists, were also extracted. The adaptive imputation strategy was designed based on a hybrid approach. The comorbidity patterns of patients were transformed into latent patterns and then clustered. Imputation was performed on a cluster of patients for each cohort independently to show the generalizability of the method. The results were compared with imputation applied to the complete dataset without incorporating the information from comorbidity patterns. RESULTS: We analyzed a total of 67,445 patients (11,230 IBD patients, 10,000 OA patients, and 46,215 patients tested for C. difficile infection). We extracted 495 LOINC and 11,230 diagnosis codes for the IBD cohort, 8160 diagnosis codes for the Cdiff cohort, and 2042 diagnosis codes for the OA cohort based on the primary/secondary diagnosis and active problem list in the EHR. Overall, the most improvement from this strategy was observed when the laboratory measures had a higher level of missingness. The best root mean square error (RMSE) difference for each dataset was recorded as -35.5 for the Cdiff, -8.3 for the IBD, and -11.3 for the OA dataset. CONCLUSIONS: An adaptive imputation strategy designed specifically for EHR that uses complementary information from the clinical profile of the patient can be used to improve the imputation of missing laboratory values, especially when laboratory codes with high levels of missingness are included in the analysis.

Decoding of single-trial EEG reveals unique states of functional brain connectivity that drive rapid speech categorization decisions.

OBJECTIVE: Categorical perception (CP) is an inherent property of speech perception. The response time (RT) of listeners' perceptual speech identification is highly sensitive to individual differences. While the neural correlates of CP have been well studied in terms of the regional contributions of the brain to behavior, functional connectivity patterns that signify individual differences in listeners' speed (RT) for speech categorization is less clear. In this study, we introduce a novel approach to address these questions. APPROACH: We applied several computational approaches to the EEG, including graph mining, machine learning (i.e., support vector machine), and stability selection to investigate the unique brain states (functional neural connectivity) that predict the speed of listeners' behavioral decisions. MAIN RESULTS: We infer that (i) the listeners' perceptual speed is directly related to dynamic variations in their brain connectomics, (ii) global network assortativity and efficiency distinguished fast, medium, and slow RTs, (iii) the functional network underlying speeded decisions increases in negative assortativity (i.e., became disassortative) for slower RTs, (iv) slower categorical speech decisions cause excessive use of neural resources and more aberrant information flow within the CP circuitry, (v) slower responders tended to utilize functional brain networks excessively (or inappropriately) whereas fast responders (with lower global efficiency) utilized the same neural pathways but with more restricted organization. SIGNIFICANCE: Findings show that neural classifiers (SVM) coupled with stability selection correctly classify behavioral RTs from functional connectivity alone with over 92% accuracy (AUC = 0.9). Our results corroborate previous studies by supporting the engagement of similar temporal (STG), parietal, motor, and prefrontal regions in CP using an entirely data-driven approach.

Age-related hearing loss increases full-brain connectivity while reversing directed signaling within the dorsal-ventral pathway for speech.

Speech comprehension difficulties are ubiquitous to aging and hearing loss, particularly in noisy environments. Older adults' poorer speech-in-noise (SIN) comprehension has been related to abnormal neural representations within various nodes (regions) of the speech network, but how senescent changes in hearing alter the transmission of brain signals remains unspecified. We measured electroencephalograms in older adults with and without mild hearing loss during a SIN identification task. Using functional connectivity and graph-theoretic analyses, we show that hearing-impaired (HI) listeners have more extended (less integrated) communication pathways and less efficient information exchange among widespread brain regions (larger network eccentricity) than their normal-hearing (NH) peers. Parameter optimized support vector machine classifiers applied to EEG connectivity data showed hearing status could be decoded (> 85% accuracy) solely using network-level descriptions of brain activity, but classification was particularly robust using left hemisphere connections. Notably, we found a reversal in directed neural signaling in left hemisphere dependent on hearing status among specific connections within the dorsal-ventral speech pathways. NH listeners showed an overall net "bottom-up" signaling directed from auditory cortex (A1) to inferior frontal gyrus (IFG; Broca's area), whereas the HI group showed the reverse signal (i.e., "top-down" Broca's → A1). A similar flow reversal was noted between left IFG and motor cortex. Our full-brain connectivity results demonstrate that even mild forms of hearing loss alter how the brain routes information within the auditory-linguistic-motor loop.

Early Imaging Based Predictive Modeling of Cognitive Performance Following Therapy for Childhood ALL.

In the United States, Acute Lymphoblastic Leukemia (ALL), the most common child and adolescent malignancy, accounts for roughly 25% of childhood cancers diagnosed annually with a 5-year survival rate as high as 94% [1]. This improved survival rate comes with an increased risk for delayed neurocognitive effects in attention, working memory, and processing speed [2]. Predictive modeling and characterization of neurocognitive effects are critical to inform the family and also to identify patients for interventions targeting. Current state-of-the-art methods mainly use hypothesis-driven statistical testing methods to characterize and model such cognitive events. While these techniques have proven to be useful in understanding cognitive abilities, they are inadequate in explaining causal relationships, as well as individuality and variations. In this study, we developed multivariate data-driven models to measure the late neurocognitive effects of ALL patients using behavioral phenotypes, Diffusion Tensor Magnetic Resonance Imaging (DTI) based tractography data, morphometry statistics, tractography measures, behavioral, and demographic variables. Alongside conventional machine learning and graph mining, we adopted "Stability Selection" to select the most relevant features and choose models that are consistent over a range of parameters. The proposed approach demonstrated substantially improved accuracy (13% - 26%) over existing models and also yielded relevant features that were verified by domain experts.

Low-voltage fast seizures in humans begin with increased interneuron firing.

OBJECTIVE: Intracellular recordings from cells in entorhinal cortex tissue slices show that low-voltage fast (LVF) onset seizures are generated by inhibitory events. Here, we determined whether increased firing of interneurons occurs at the onset of spontaneous mesial-temporal LVF seizures recorded in patients. METHODS: The seizure onset zone (SOZ) was identified using visual inspection of the intracranial electroencephalogram. We used wavelet clustering and temporal autocorrelations to characterize changes in single-unit activity during the onset of LVF seizures recorded from microelectrodes in mesial-temporal structures. Action potentials generated by principal neurons and interneurons (ie, putative excitatory and inhibitory neurons) were distinguished using waveform morphology and K-means clustering. RESULTS: From a total of 200 implanted microelectrodes in 9 patients during 13 seizures, we isolated 202 single units; 140 (69.3%) of these units were located in the SOZ, and 40 (28.57%) of them were classified as inhibitory. The waveforms of both excitatory and inhibitory units remained stable during the LVF epoch (p > > 0.05). In the mesial-temporal SOZ, inhibitory interneurons increased their firing rate during LVF seizure onset (p < 0.01). Excitatory neuron firing rates peaked 10 seconds after the inhibitory neurons (p < 0.01). During LVF spread to the contralateral mesial temporal lobe, an increase in inhibitory neuron firing rate was also observed (p < 0.01). INTERPRETATION: Our results suggest that seizure generation and spread during spontaneous mesial-temporal LVF onset events in humans may result from increased inhibitory neuron firing that spawns a subsequent increase in excitatory neuron firing and seizure evolution. Ann Neurol 2018;84:588-600.

Identifying seizure onset zone from electrocorticographic recordings: A machine learning approach based on phase locking value.

PURPOSE: Using a novel technique based on phase locking value (PLV), we investigated the potential for features extracted from electrocorticographic (ECoG) recordings to serve as biomarkers to identify the seizure onset zone (SOZ). METHODS: We computed the PLV between the phase of the amplitude of high gamma activity (80-150Hz) and the phase of lower frequency rhythms (4-30Hz) from ECoG recordings obtained from 10 patients with epilepsy (21 seizures). We extracted five features from the PLV and used a machine learning approach based on logistic regression to build a model that classifies electrodes as SOZ or non-SOZ. RESULTS: More than 96% of electrodes identified as the SOZ by our algorithm were within the resected area in six seizure-free patients. In four non-seizure-free patients, more than 31% of the identified SOZ electrodes by our algorithm were outside the resected area. In addition, we observed that the seizure outcome in non-seizure-free patients correlated with the number of non-resected SOZ electrodes identified by our algorithm. CONCLUSION: This machine learning approach, based on features extracted from the PLV, effectively identified electrodes within the SOZ. The approach has the potential to assist clinicians in surgical decision-making when pre-surgical intracranial recordings are utilized.

Empirical study using network of semantically related associations in bridging the knowledge gap.

BACKGROUND: The data overload has created a new set of challenges in finding meaningful and relevant information with minimal cognitive effort. However designing robust and scalable knowledge discovery systems remains a challenge. Recent innovations in the (biological) literature mining tools have opened new avenues to understand the confluence of various diseases, genes, risk factors as well as biological processes in bridging the gaps between the massive amounts of scientific data and harvesting useful knowledge. METHODS: In this paper, we highlight some of the findings using a text analytics tool, called ARIANA--Adaptive Robust and Integrative Analysis for finding Novel Associations. RESULTS: Empirical study using ARIANA reveals knowledge discovery instances that illustrate the efficacy of such tool. For example, ARIANA can capture the connection between the drug hexamethonium and pulmonary inflammation and fibrosis that caused the tragic death of a healthy volunteer in a 2001 John Hopkins asthma study, even though the abstract of the study was not part of the semantic model. CONCLUSION: An integrated system, such as ARIANA, could assist the human expert in exploratory literature search by bringing forward hidden associations, promoting data reuse and knowledge discovery as well as stimulating interdisciplinary projects by connecting information across the disciplines.

Spectrotemporal dynamics of the EEG during working memory encoding and maintenance predicts individual behavioral capacity.

We investigated the effect of memory load on encoding and maintenance of information in working memory. Electroencephalography (EEG) signals were recorded while participants performed a modified Sternberg visual memory task. Independent component analysis (ICA) was used to factorise the EEG signals into distinct temporal activations to perform spectrotemporal analysis and localisation of source activities. We found 'encoding' and 'maintenance' operations were correlated with negative and positive changes in α-band power, respectively. Transient activities were observed during encoding of information in the bilateral cuneus, precuneus, inferior parietal gyrus and fusiform gyrus, and a sustained activity in the inferior frontal gyrus. Strong correlations were also observed between changes in α-power and behavioral performance during both encoding and maintenance. Furthermore, it was also found that individuals with higher working memory capacity experienced stronger neural oscillatory responses during the encoding of visual objects into working memory. Our results suggest an interplay between two distinct neural pathways and different spatiotemporal operations during the encoding and maintenance of information which predict individual differences in working memory capacity observed at the behavioral level.

Evaluation of supervised and unsupervised 3D star visualisation algorithms.

The 3D Star Coordinate Projection (3DSCP) visualisation algorithm has been developed to address the following key issues: choosing the projection configuration autonomously. preserving the data topology after projection. enhancing resolution. A supervised version of 3DSCP (S3DSCP) is also introduced to improve the computational efficiency of 3DSCP. Comparison with other linear, non-linear and axis-based techniques is performed to illustrate the efficacy of the 3DSCP and S3DSCP methods. Empirical analyses indicate that the 3DSCP and S3DSCP algorithms find hidden patterns in data while overcoming limitations of other techniques.

An automated framework for hypotheses generation using literature.

BACKGROUND: In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF) finds "crisp semantic associations" among entities of interest - that is a step towards bridging such gaps. METHODOLOGY: The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect "crisp" associations, and making assertions about entities (such as disease X is associated with a set of factors Z). RESULTS: Pilot studies were performed using two diseases. A comparative analysis of the computed "associations" and "assertions" with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture "crisp" direct and indirect associations, and provide knowledge discovery on demand. CONCLUSIONS: The proposed framework is fast, efficient, and robust in generating new hypotheses to identify factors associated with a disease. A full integrated Web service application is being developed for wide dissemination of the HGF. A large-scale study by the domain experts and associated researchers is underway to validate the associations and assertions computed by the HGF.

Prediction of membrane proteins using split amino acid and ensemble classification.

Knowledge of the types of membrane protein provides useful clues in deducing the functions of uncharacterized membrane proteins. An automatic method for efficiently identifying uncharacterized proteins is thus highly desirable. In this work, we have developed a novel method for predicting membrane protein types by exploiting the discrimination capability of the difference in amino acid composition at the N and C terminus through split amino acid composition (SAAC). We also show that the ensemble classification can better exploit this discriminating capability of SAAC. In this study, membrane protein types are classified using three feature extraction and several classification strategies. An ensemble classifier Mem-EnsSAAC is then developed using the best feature extraction strategy. Pseudo amino acid (PseAA) composition, discrete wavelet analysis (DWT), SAAC, and a hybrid model are employed for feature extraction. The nearest neighbor, probabilistic neural network, support vector machine, random forest, and Adaboost are used as individual classifiers. The predicted results of the individual learners are combined using genetic algorithm to form an ensemble classifier, Mem-EnsSAAC yielding an accuracy of 92.4 and 92.2% for the Jackknife and independent dataset test, respectively. Performance measures such as MCC, sensitivity, specificity, F-measure, and Q-statistics show that SAAC-based prediction yields significantly higher performance compared to PseAA- and DWT-based systems, and is also the best reported so far. The proposed Mem-EnsSAAC is able to predict the membrane protein types with high accuracy and consequently, can be very helpful in drug discovery. It can be accessed at http://111.68.99.218/membrane.

Fuzzy-adaptive-subspace-iteration-based two-way clustering of microarray data.

This paper presents Fuzzy-Adaptive-Subspace-Iteration-based Two-way Clustering (FASIC) of microarray data for finding differentially expressed genes (DEGs) from two-sample microarray experiments. The concept of fuzzy membership is introduced to transform the hard adaptive subspace iteration (ASI) algorithm into a fuzzy-ASI algorithm to perform two-way clustering. The proposed approach follows a progressive framework to assign a relevance value to genes associated with each cluster. Subsequently, each gene cluster is scored and ranked based on its potential to provide a correct classification of the sample classes. These ranks are converted into P values using the R-test, and the significance of each gene is determined. A fivefold validation is performed on the DEGs selected using the proposed approach. Empirical analyses on a number of simulated microarray data sets are conducted to quantify the results obtained using the proposed approach. To exemplify the efficacy of the proposed approach, further analyses on different real microarray data sets are also performed.

Semantically linking and browsing PubMed abstracts with gene ontology.

BACKGROUND: The technological advances in the past decade have lead to massive progress in the field of biotechnology. The documentation of the progress made exists in the form of research articles. The PubMed is the current most used repository for bio-literature. PubMed consists of about 17 million abstracts as of 2007 that require methods to efficiently retrieve and browse large volume of relevant information. The State-of-the-art technologies such as GOPubmed use simple keyword-based techniques for retrieving abstracts from the PubMed and linking them to the Gene Ontology (GO). This paper changes the paradigm by introducing semantics enabled technique to link the PubMed to the Gene Ontology, called, SEGOPubmed for ontology-based browsing. Latent Semantic Analysis (LSA) framework is used to semantically interface PubMed abstracts to the Gene Ontology. RESULTS: The Empirical analysis is performed to compare the performance of the SEGOPubmed with the GOPubmed. The analysis is initially performed using a few well-referenced query words. Further, statistical analysis is performed using GO curated dataset as ground truth. The analysis suggests that the SEGOPubmed performs better than the classic GOPubmed as it incorporates semantics. CONCLUSIONS: The LSA technique is applied on the PubMed abstracts obtained based on the user query and the semantic similarity between the query and the abstracts. The analyses using well-referenced keywords show that the proposed semantic-sensitive technique outperformed the string comparison based techniques in associating the relevant abstracts to the GO terms. The SEGOPubmed also extracted the abstracts in which the keywords do not appear in isolation (i.e. they appear in combination with other terms) that could not be retrieved by simple term matching techniques.