Publications
Open-source, community-driven microfluidics with Metafluidics
June 7, 2017
Journal Article
Published in:
Nat. Biotechnol., Vol. 35, No. 6, 7 June 2017, pp. 523-9.
Topic:
R&D area:
Summary
Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. We use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.
Summary
Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on...
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Detecting virus exposure during the pre-symptomatic incubation period using physiological data
March 3, 2017
Journal Article
Published in:
Science Translational Medicine (submitted), 3 March 2017.
Summary
Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Using high-resolution physiological data from non-human primate studies of Ebola and Marburg viruses, we pre-processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm. In most subjects detection is achieved well before the onset of fever; subject cross-validation lead to 52±14h mean early detection (at >0.90 area under the receiver-operating characteristic curve). Cross-cohort tests across pathogens and exposure routes also lead to successful early detection (28±16h and 43±22h, respectively). We discuss which physiological indicators are most informative for early detection and options for extending this capability to lower data resolution and wearable, non-invasive sensors.
Summary
Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning method to better detect asymptomatic states during...
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Building low-power trustworthy systems: cyber-security considerations for real-time physiological status monitoring
November 1, 2016
Conference Paper
Published in:
IEEE MILCOM, 1-3 November 2016.
Summary
Real-time monitoring of physiological data can reduce the likelihood of injury in noncombat military personnel and first-responders. MIT Lincoln Laboratory is developing a tactical Real-Time Physiological Status Monitoring (RT-PSM) system architecture and reference implementation named OBAN (Open Body Area Network), the purpose of which is to provide an open, government-owned framework for integrating multiple wearable sensors and applications. The OBAN implementation accepts data from various sensors enabling calculation of physiological strain information which may be used by squad leaders or medics to assess the team's health and enhance safety and effectiveness of mission execution. Security in terms of measurement integrity, confidentiality, and authenticity is an area of interest because OBAN system components exchange sensitive data in contested environments. In this paper, we analyze potential cyber-security threats and their associated risks to a generalized version of the OBAN architecture and identify directions for future research. The threat analysis is intended to inform the development of secure RT-PSM architectures and implementations.
Summary
Real-time monitoring of physiological data can reduce the likelihood of injury in noncombat military personnel and first-responders. MIT Lincoln Laboratory is developing a tactical Real-Time Physiological Status Monitoring (RT-PSM) system architecture and reference implementation named OBAN (Open Body Area Network), the purpose of which is to provide an open, government-owned...
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Detecting depression using vocal, facial and semantic communication cues
October 15, 2016
Conference Paper
Published in:
ACM Multimedia Conf. AVEC Workshop, 15-19 October 2016.
Summary
Major depressive disorder (MDD) is known to result in neurophysiological and neurocognitive changes that affect control of motor, linguistic, and cognitive functions. MDD's impact on these processes is reflected in an individual's communication via coupled mechanisms: vocal articulation, facial gesturing and choice of content to convey in a dialogue. In particular, MDD-induced neurophysiological changes are associated with a decline in dynamics and coordination of speech and facial motor control, while neurocognitive changes influence dialogue semantics. In this paper, biomarkers are derived from all of these modalities, drawing first from previously developed neurophysiologically motivated speech and facial coordination and timing features. In addition, a novel indicator of lower vocal tract constriction in articulation is incorporated that relates to vocal projection. Semantic features are analyzed for subject/avatar dialogue content using a sparse coded lexical embedding space, and for contextual clues related to the subject's present or past depression status. The features and depression classification system were developed for the 6th International Audio/Video Emotion Challenge (AVEC), which provides data consisting of audio, video-based facial action units, and transcribed text of individuals communicating with the human-controlled avatar. A clinical Patient Health Questionnaire (PHQ) score and binary depression decision are provided for each participant. PHQ predictions were obtained by fusing outputs from a Gaussian staircase regressor for each feature set, with results on the development set of mean F1=0.81, RMSE=5.31, and MAE=3.34. These compare favorably to the challenge baseline development results of mean F1=0.73, RMSE=6.62, and MAE=5.52. On test set evaluation, our system obtained a mean F1=0.70, which is similar to the challenge baseline test result. Future work calls for consideration of joint feature analyses across modalities in an effort to detect neurological disorders based on the interplay of motor, linguistic, affective, and cognitive components of communication.
Summary
Major depressive disorder (MDD) is known to result in neurophysiological and neurocognitive changes that affect control of motor, linguistic, and cognitive functions. MDD's impact on these processes is reflected in an individual's communication via coupled mechanisms: vocal articulation, facial gesturing and choice of content to convey in a dialogue. In...
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Benchmarking SciDB data import on HPC systems
September 13, 2016
Conference Paper
Published in:
HPEC 2016: IEEE Conf. on High Performance Extreme Computing, 13-15 September 2016.
Summary
SciDB is a scalable, computational database management system that uses an array model for data storage. The array data model of SciDB makes it ideally suited for storing and managing large amounts of imaging data. SciDB is designed to support advanced analytics in database, thus reducing the need for extracting data for analysis. It is designed to be massively parallel and can run on commodity hardware in a high performance computing (HPC) environment. In this paper, we present the performance of SciDB using simulated image data. The Dynamic Distributed Dimensional Data Model (D4M) software is used to implement the benchmark on a cluster running the MIT SuperCloud software stack. A peak performance of 2.2M database inserts per second was achieved on a single node of this system. We also show that SciDB and the D4M toolbox provide more efficient ways to access random sub-volumes of massive datasets compared to the traditional approaches of reading volumetric data from individual files. This work describes the D4M and SciDB tools we developed and presents the initial performance results. This performance was achieved by using parallel inserts, a in-database merging of arrays as well as supercomputing techniques, such as distributed arrays and single-program-multiple-data programming.
Summary
SciDB is a scalable, computational database management system that uses an array model for data storage. The array data model of SciDB makes it ideally suited for storing and managing large amounts of imaging data. SciDB is designed to support advanced analytics in database, thus reducing the need for extracting...
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Relation of automatically extracted formant trajectories with intelligibility loss and speaking rate decline in amyotrophic lateral sclerosis
September 8, 2016
Conference Paper
Published in:
INTERSPEECH 2016: 16th Annual Conf. of the Int. Speech Communication Assoc., 8-12 September 2016.
Summary
Effective monitoring of bulbar disease progression in persons with amyotrophic lateral sclerosis (ALS) requires rapid, objective, automatic assessment of speech loss. The purpose of this work was to identify acoustic features that aid in predicting intelligibility loss and speaking rate decline in individuals with ALS. Features were derived from statistics of the first (F1) and second (F2) formant frequency trajectories and their first and second derivatives. Motivated by a possible link between components of formant dynamics and specific articulator movements, these features were also computed for low-pass and high-pass filtered formant trajectories. When compared to clinician-rated intelligibility and speaking rate assessments, F2 features, particularly mean F2 speed and a novel feature, mean F2 acceleration, were most strongly correlated with intelligibility and speaking rate, respectively (Spearman correlations > 0.70, p < 0.0001). These features also yielded the best predictions in regression experiments (r > 0.60, p < 0.0001). Comparable results were achieved using low-pass filtered F2 trajectory features, with higher correlations and lower prediction errors achieved for speaking rate over intelligibility. These findings suggest information can be exploited in specific frequency components of formant trajectories, with implications for automatic monitoring of ALS.
Summary
Effective monitoring of bulbar disease progression in persons with amyotrophic lateral sclerosis (ALS) requires rapid, objective, automatic assessment of speech loss. The purpose of this work was to identify acoustic features that aid in predicting intelligibility loss and speaking rate decline in individuals with ALS. Features were derived from statistics...
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Relating estimated cyclic spectral peak frequency to measured epilarynx length using magnetic resonance imaging
September 8, 2016
Conference Paper
Published in:
INTERSPEECH 2016: 16th Annual Conf. of the Int. Speech Communication Assoc., 8-12 September 2016.
Summary
The epilarynx plays an important role in speech production, carrying information about the individual speaker and manner of articulation. However, precise acoustic behavior of this lower vocal tract structure is difficult to establish. Focusing on acoustics observable in natural speech, recent spectral processing techniques isolate a unique resonance with characteristics of the epilarynx previously shown via simulation, specifically cyclicity (i.e. energy differences between the closed and open phases of the glottal cycle) in a 3-5kHz region observed across vowels. Using Magnetic Resonance Imaging (MRI), the present work relates this estimated cyclic peak frequency to measured epilarynx length. Assuming a simple quarter wavelength relationship, the cavity length estimated from the cyclic peak frequency is shown to be directly proportional (linear fit slope =1.1) and highly correlated (p = 0.85, pval<10^?4) to the measured epilarynx length across speakers. Results are discussed, as are implications in speech science and application domains.
Summary
The epilarynx plays an important role in speech production, carrying information about the individual speaker and manner of articulation. However, precise acoustic behavior of this lower vocal tract structure is difficult to establish. Focusing on acoustics observable in natural speech, recent spectral processing techniques isolate a unique resonance with characteristics...
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A vocal modulation model with application to predicting depression severity
June 14, 2016
Conference Paper
Published in:
13th IEEE Int. Conf. on Wearable and Implantable Body Sensor Networks, BSN 2016, 14-17 June 2016.
Summary
Speech provides a potential simple and noninvasive "on-body" means to identify and monitor neurological diseases. Here we develop a model for a class of vocal biomarkers exploiting modulations in speech, focusing on Major Depressive Disorder (MDD) as an application area. Two model components contribute to the envelope of the speech waveform: amplitude modulation (AM) from respiratory muscles, and AM from interaction between vocal tract resonances (formants) and frequency modulation in vocal fold harmonics. Based on the model framework, we test three methods to extract envelopes capturing these modulations of the third formant for synthesized sustained vowels. Using subsequent modulation features derived from the model, we predict MDD severity scores with a Gaussian Mixture Model. Performing global optimization over classifier parameters and number of principal components, we evaluate performance of the features by examining the root-mean-squared error (RMSE), mean absolute error (MAE), and Spearman correlation between the actual and predicted MDD scores. We achieved RMSE and MAE values 10.32 and 8.46, respectively (Spearman correlation=0.487, p<0.001), relative to a baseline RMSE of 11.86 and MAE of 10.05, obtained by predicting the mean MDD severity score. Ultimately, our model provides a framework for detecting and monitoring vocal modulations that could also be applied to other neurological diseases.
Summary
Speech provides a potential simple and noninvasive "on-body" means to identify and monitor neurological diseases. Here we develop a model for a class of vocal biomarkers exploiting modulations in speech, focusing on Major Depressive Disorder (MDD) as an application area. Two model components contribute to the envelope of the speech...
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D4M and large array databases for management and analysis of large biomedical imaging data
January 28, 2016
Conference Paper
Published in:
North East Database Day 2016, 28 January 2016.
Summary
Advances in medical imaging technologies have enabled the acquisition of increasingly large datasets. Current state-of-the-art confocal or multi-photon imaging technology can produce biomedical datasets in excess of 1 TB per dataset. Typical approaches for analyzing large datasets rely on downsampling the original datasets or leveraging distributed computing resources where small subsets of images are processed independently. These approaches require significant overhead on the part of the programmer to load the desired sub-volume from an array of image files into memory. Databases are well suited for indexing and retrieving components of very large datasets and show significant promise for the analysis of 3D volumetric images. In particular, array-based databases such as SciDB utilize an architecture that supports massive parallel processing while also providing database services such as data management and fast parallel queries. In this paper, we will present a new set of tools that leverage the D4M (Dynamic Distributed Dimensional Data Model) toolbox for analyzing giga-voxel biomedical datasets. By combining SciDB and the D4M toolbox, we demonstrate that we can access large volumetric data and perform large-scale bioinformatics analytics efficiently and interactively. We show that it is possible to achieve an ingest rate of 2.8 million entries per second for importing large datasets into SciDB. These tools provide more efficient ways to access random sub-volumes of massive datasets and to process the information that typically cannot be loaded into memory. This work describes the D4M and SciDB tools that we developed and presents the initial performance results.
Summary
Advances in medical imaging technologies have enabled the acquisition of increasingly large datasets. Current state-of-the-art confocal or multi-photon imaging technology can produce biomedical datasets in excess of 1 TB per dataset. Typical approaches for analyzing large datasets rely on downsampling the original datasets or leveraging distributed computing resources where small...
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Assessing functional neural connectivity as an indicator of cognitive performance
December 11, 2015
Conference Paper
Published in:
5th NIPS Workshop on Machine Learning and Interpretation in Neuroimaging, MLINI 2015, 11-12 December 2015.
Topic:
R&D area:
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Summary
Studies in recent years have demonstrated that neural organization and structure impact an individual's ability to perform a given task. Specifically, individuals with greater neural efficiency have been shown to outperform those with less organized functional structure. In this work, we compare the predictive ability of properties of neural connectivity on a working memory task. We provide two novel approaches for characterizing functional network connectivity from electroencephalography (EEG), and compare these features to the average power across frequency bands in EEG channels. Our first novel approach represents functional connectivity structure through the distribution of eigenvalues making up channel coherence matrices in multiple frequency bands. Our second approach creates a connectivity network at each frequency band, and assesses variability in average path lengths of connected components and degree across the network. Failures in digit and sentence recall on single trials are detected using a Gaussian classifier for each feature set, at each frequency band. The classifier results are then fused across frequency bands, with the resulting detection performance summarized using the area under the receiver operating characteristic curve (AUC) statistic. Fused AUC results of 0.63/0.58/0.61 for digit recall failure and 0.58/0.59/0.54 for sentence recall failure are obtained from the connectivity structure, graph variability, and channel power features respectively.
Summary
Studies in recent years have demonstrated that neural organization and structure impact an individual's ability to perform a given task. Specifically, individuals with greater neural efficiency have been shown to outperform those with less organized functional structure. In this work, we compare the predictive ability of properties of neural connectivity...
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