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Large-scale Bayesian kinship analysis

Summary

Kinship prediction in forensics is limited to first degree relatives due to the small number of short tandem repeat loci characterized. The Genetic Chain Rule for Probabilistic Kinship Estimation can leverage large panels of single nucleotide polymorphisms (SNPs) or sets of sequence linked SNPs, called haploblocks, to estimate more distant relationships between individuals. This method uses allele frequencies and Markov Chain Monte Carlo methods to determine kinship probabilities. Allele frequencies are a crucial input to this method. Since these frequencies are estimated from finite populations and many alleles are rare, a Bayesian extension to the algorithm has been developed to determine credible intervals for kinship estimates as a function of the certainty in allele frequency estimates. Generation of sufficiently large samples to accurately estimate credible intervals can take significant computational resources. In this paper, we leverage hundreds of compute cores to generate large numbers of Dirichlet random samples for Bayesian kinship prediction. We show that it is possible to generate 2,097,152 random samples on 32,768 cores at a rate of 29.68 samples per second. The ability to generate extremely large number of samples enables the computation of more statistically significant results from a Bayesian approach to kinship analysis.
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Summary

Kinship prediction in forensics is limited to first degree relatives due to the small number of short tandem repeat loci characterized. The Genetic Chain Rule for Probabilistic Kinship Estimation can leverage large panels of single nucleotide polymorphisms (SNPs) or sets of sequence linked SNPs, called haploblocks, to estimate more distant...

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A cloud-based brain connectivity analysis tool

Summary

With advances in high throughput brain imaging at the cellular and sub-cellular level, there is growing demand for platforms that can support high performance, large-scale brain data processing and analysis. In this paper, we present a novel pipeline that combines Accumulo, D4M, geohashing, and parallel programming to manage large-scale neuron connectivity graphs in a cloud environment. Our brain connectivity graph is represented using vertices (fiber start/end nodes), edges (fiber tracks), and the 3D coordinates of the fiber tracks. For optimal performance, we take the hybrid approach of storing vertices and edges in Accumulo and saving the fiber track 3D coordinates in flat files. Accumulo database operations offer low latency on sparse queries while flat files offer high throughput for storing, querying, and analyzing bulk data. We evaluated our pipeline by using 250 gigabytes of mouse neuron connectivity data. Benchmarking experiments on retrieving vertices and edges from Accumulo demonstrate that we can achieve 1-2 orders of magnitude speedup in retrieval time when compared to the same operation from traditional flat files. The implementation of graph analytics such as Breadth First Search using Accumulo and D4M offers consistent good performance regardless of data size and density, thus is scalable to very large dataset. Indexing of neuron subvolumes is simple and logical with geohashing-based binary tree encoding. This hybrid data management backend is used to drive an interactive web-based 3D graphical user interface, where users can examine the 3D connectivity map in a Google Map-like viewer. Our pipeline is scalable and extensible to other data modalities.
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Summary

With advances in high throughput brain imaging at the cellular and sub-cellular level, there is growing demand for platforms that can support high performance, large-scale brain data processing and analysis. In this paper, we present a novel pipeline that combines Accumulo, D4M, geohashing, and parallel programming to manage large-scale neuron...

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A linear algebra approach to fast DNA mixture analysis using GPUs

Published in:
HPEC 2017: IEEE Conf. on High Performance Extreme Computing, 12-14 September 2017.

Summary

Analysis of DNA samples is an important step in forensics, and the speed of analysis can impact investigations. Comparison of DNA sequences is based on the analysis of short tandem repeats (STRs), which are short DNA sequences of 2-5 base pairs. Current forensics approaches use 20 STR loci for analysis. The use of single nucleotide polymorphisms (SNPs) has utility for analysis of complex DNA mixtures. The use of tens of thousands of SNPs loci for analysis poses significant computational challenges because the forensic analysis scales by the product of the loci count and number of DNA samples to be analyzed. In this paper, we discuss the implementation of a DNA sequence comparison algorithm by re-casting the algorithm in terms of linear algebra primitives. By developing an overloaded matrix multiplication approach to DNA comparisons, we can leverage advances in GPU hardware and algorithms for Dense Generalized Matrix-Multiply (DGEMM) to speed up DNA sample comparisons. We show that it is possible to compare 2048 unknown DNA samples with 20 million known samples in under 6 seconds using a NVIDIA K80 GPU.
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Summary

Analysis of DNA samples is an important step in forensics, and the speed of analysis can impact investigations. Comparison of DNA sequences is based on the analysis of short tandem repeats (STRs), which are short DNA sequences of 2-5 base pairs. Current forensics approaches use 20 STR loci for analysis...

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Open-source, community-driven microfluidics with Metafluidics

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.
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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

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.
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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

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.
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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

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.
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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

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.
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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

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.
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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

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.
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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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