May D. Wang

CL
h-index28
23papers
523citations
Novelty44%
AI Score57

23 Papers

86.6CLMar 20Code
EvidenceRL: Reinforcing Evidence Consistency for Trustworthy Language Models

J. Ben Tamo, Yuxing Lu, Benoit L. Marteau et al.

Large Language Models (LLMs) are fluent but prone to hallucinations, producing answers that appear plausible yet are unsupported by available evidence. This failure is especially problematic in high-stakes domains where decisions must be justified by verifiable information. We introduce \textbf{EvidenceRL}, a reinforcement learning framework that enforces evidence adherence during training. EvidenceRL scores candidate responses for grounding (entailment with retrieved evidence and context) and correctness (agreement with reference answers) and optimizes the generator using Group Relative Policy Optimization (GRPO). We evaluate across two high-stakes domains, cardiac diagnosis and legal reasoning, where EvidenceRL consistently improves evidence grounding and faithfulness without sacrificing task accuracy. On cardiac diagnosis, F1@3 increases from 37.0 to 54.5 on Llama-3.2-3B while grounding ($G_{\max}@3$) rises from 47.6 to 78.2; hallucinations drop nearly 5$\times$ and evidence-supported diagnoses increase from 31.8\% to 61.6\%. On legal reasoning, EvidenceRL raises Faithfulness from 32.8\% to 67.6\% on Llama-3.1-8B, demonstrating consistent behavioral change across domains. Our code is open-sourced at https://github.com/Wizaaard/EvidenceRL.git.

CLApr 29, 2024Code
BMRetriever: Tuning Large Language Models as Better Biomedical Text Retrievers

Ran Xu, Wenqi Shi, Yue Yu et al. · gatech

Developing effective biomedical retrieval models is important for excelling at knowledge-intensive biomedical tasks but still challenging due to the deficiency of sufficient publicly annotated biomedical data and computational resources. We present BMRetriever, a series of dense retrievers for enhancing biomedical retrieval via unsupervised pre-training on large biomedical corpora, followed by instruction fine-tuning on a combination of labeled datasets and synthetic pairs. Experiments on 5 biomedical tasks across 11 datasets verify BMRetriever's efficacy on various biomedical applications. BMRetriever also exhibits strong parameter efficiency, with the 410M variant outperforming baselines up to 11.7 times larger, and the 2B variant matching the performance of models with over 5B parameters. The training data and model checkpoints are released at \url{https://huggingface.co/BMRetriever} to ensure transparency, reproducibility, and application to new domains.

CLFeb 25, 2024Code
RAM-EHR: Retrieval Augmentation Meets Clinical Predictions on Electronic Health Records

Ran Xu, Wenqi Shi, Yue Yu et al. · gatech

We present RAM-EHR, a Retrieval AugMentation pipeline to improve clinical predictions on Electronic Health Records (EHRs). RAM-EHR first collects multiple knowledge sources, converts them into text format, and uses dense retrieval to obtain information related to medical concepts. This strategy addresses the difficulties associated with complex names for the concepts. RAM-EHR then augments the local EHR predictive model co-trained with consistency regularization to capture complementary information from patient visits and summarized knowledge. Experiments on two EHR datasets show the efficacy of RAM-EHR over previous knowledge-enhanced baselines (3.4% gain in AUROC and 7.2% gain in AUPR), emphasizing the effectiveness of the summarized knowledge from RAM-EHR for clinical prediction tasks. The code will be published at \url{https://github.com/ritaranx/RAM-EHR}.

CVFeb 13
Monocular Markerless Motion Capture Enables Quantitative Assessment of Upper Extremity Reachable Workspace

Seth Donahue, J. D. Peiffer, R. Tyler Richardson et al.

To validate a clinically accessible approach for quantifying the Upper Extremity Reachable Workspace (UERW) using a single (monocular) camera and Artificial Intelligence (AI)-driven Markerless Motion Capture (MMC) for biomechanical analysis. Objective assessment and validation of these techniques for specific clinically oriented tasks are crucial for their adoption in clinical motion analysis. AI-driven monocular MMC reduces the barriers to adoption in the clinic and has the potential to reduce the overhead for analysis of this common clinical assessment. Nine adult participants with no impairments performed the standardized UERW task, which entails reaching targets distributed across a virtual sphere centered on the torso, with targets displayed in a VR headset. Movements were simultaneously captured using a marker-based motion capture system and a set of eight FLIR cameras. We performed monocular video analysis on two of these video camera views to compare a frontal and offset camera configurations. The frontal camera orientation demonstrated strong agreement with the marker-based reference, exhibiting a minimal mean bias of $0.61 \pm 0.12$ \% reachspace reached per octanct (mean $\pm$ standard deviation). In contrast, the offset camera view underestimated the percent workspace reached ($-5.66 \pm 0.45$ \% reachspace reached). Conclusion: The findings support the feasibility of a frontal monocular camera configuration for UERW assessment, particularly for anterior workspace evaluation where agreement with marker-based motion capture was highest. The overall performance demonstrates clinical potential for practical, single-camera assessments. This study provides the first validation of monocular MMC system for the assessment of the UERW task. By reducing technical complexity, this approach enables broader implementation of quantitative upper extremity mobility assessment.

41.2CVApr 10
RobustMedSAM: Degradation-Resilient Medical Image Segmentation via Robust Foundation Model Adaptation

Jieru Li, Matthew Chen, Micky C. Nnamdi et al.

Medical image segmentation models built on Segment Anything Model (SAM) achieve strong performance on clean benchmarks, yet their reliability often degrades under realistic image corruptions such as noise, blur, motion artifacts, and modality-specific distortions. Existing approaches address either medical-domain adaptation or corruption robustness, but not both jointly. In SAM, we find that these capabilities are concentrated in complementary modules: the image encoder preserves medical priors, while the mask decoder governs corruption robustness. Motivated by this observation, we propose RobustMedSAM, which adopts module-wise checkpoint fusion by initializing the image encoder from MedSAM and the mask decoder from RobustSAM under a shared ViT-B architecture. We then fine-tune only the mask decoder on 35 medical datasets from MedSegBench, spanning six imaging modalities and 12 corruption types, while freezing the remaining components to preserve pretrained medical representations. We additionally investigate an SVD-based parameter-efficient variant for limited encoder adaptation. Experiments on both in-distribution and out-of-distribution benchmarks show that RobustMedSAM improves degraded-image Dice from 0.613 to 0.719 (+0.106) over SAM, demonstrating that structured fusion of complementary pretrained models is an effective and practical approach for robust medical image segmentation.

28.4LGApr 9
Tree-of-Evidence: Efficient "System 2" Search for Faithful Multimodal Grounding

Micky C. Nnamdi, Benoit L. Marteau, Yishan Zhong et al.

Large Multimodal Models (LMMs) achieve state-of-the-art performance in high-stakes domains like healthcare, yet their reasoning remains opaque. Current interpretability methods, such as attention mechanisms or post-hoc saliency, often fail to faithfully represent the model's decision-making process, particularly when integrating heterogeneous modalities like time-series and text. We introduce Tree-of-Evidence (ToE), an inference-time search algorithm that frames interpretability as a discrete optimization problem. Rather than relying on soft attention weights, ToE employs lightweight Evidence Bottlenecks that score coarse groups or units of data (e.g., vital-sign windows, report sentences) and performs a beam search to identify the compact evidence set required to reproduce the model's prediction. We evaluate ToE across six tasks spanning three datasets and two domains: four clinical prediction tasks on MIMIC-IV, cross-center validation on eICU, and non-clinical fault detection on LEMMA-RCA. ToE produces auditable evidence traces while maintaining predictive performance, retaining over 0.98 of full-model AUROC with as few as five evidence units across all settings. Under sparse evidence budgets, ToE achieves higher decision agreement and lower probability fidelity error than other approaches. Qualitative analyses show that ToE adapts its search strategy: it often resolves straightforward cases using only vitals, while selectively incorporating text when physiological signals are ambiguous. ToE therefore provides a practical mechanism for auditing multimodal models by revealing which discrete evidence units support each prediction.

LGSep 24, 2025Code
Causal Machine Learning for Surgical Interventions

J. Ben Tamo, Nishant S. Chouhan, Micky C. Nnamdi et al.

Surgical decision-making is complex and requires understanding causal relationships between patient characteristics, interventions, and outcomes. In high-stakes settings like spinal fusion or scoliosis correction, accurate estimation of individualized treatment effects (ITEs) remains limited due to the reliance on traditional statistical methods that struggle with complex, heterogeneous data. In this study, we develop a multi-task meta-learning framework, X-MultiTask, for ITE estimation that models each surgical decision (e.g., anterior vs. posterior approach, surgery vs. no surgery) as a distinct task while learning shared representations across tasks. To strengthen causal validity, we incorporate the inverse probability weighting (IPW) into the training objective. We evaluate our approach on two datasets: (1) a public spinal fusion dataset (1,017 patients) to assess the effect of anterior vs. posterior approaches on complication severity; and (2) a private AIS dataset (368 patients) to analyze the impact of posterior spinal fusion (PSF) vs. non-surgical management on patient-reported outcomes (PROs). Our model achieves the highest average AUC (0.84) in the anterior group and maintains competitive performance in the posterior group (0.77). It outperforms baselines in treatment effect estimation with the lowest overall $ε_{\text{NN-PEHE}}$ (0.2778) and $ε_{\text{ATE}}$ (0.0763). Similarly, when predicting PROs in AIS, X-MultiTask consistently shows superior performance across all domains, with $ε_{\text{NN-PEHE}}$ = 0.2551 and $ε_{\text{ATE}}$ = 0.0902. By providing robust, patient-specific causal estimates, X-MultiTask offers a powerful tool to advance personalized surgical care and improve patient outcomes. The code is available at https://github.com/Wizaaard/X-MultiTask.

CLJun 4, 2025Code
MedAgentGym: A Scalable Agentic Training Environment for Code-Centric Reasoning in Biomedical Data Science

Ran Xu, Yuchen Zhuang, Yishan Zhong et al. · gatech

We introduce MedAgentGym, a scalable and interactive training environment designed to enhance coding-based biomedical reasoning capabilities in large language model (LLM) agents. MedAgentGym comprises 72,413 task instances across 129 categories derived from 12 authentic real-world biomedical scenarios. Tasks are encapsulated within executable sandbox environments, each featuring detailed task specifications, interactive feedback mechanisms, verifiable ground truth annotations, and scalable training trajectory generation. Extensive benchmarking of 29 LLMs reveals substantial performance disparities in biomedical data science between commercial and open-source LLMs. Leveraging efficient multi-threaded and multi-turn trajectory sampling in MedAgentGym, Med-Copilot achieves performance gains of +43.02% and +45.28% from offline and online reinforcement learning, respectively, demonstrating MedAgentGym as an effective training ground while establishing itself as a cost-effective, privacy-preserving alternative competitive with proprietary LLMs (gpt-4o). By offering a unified execution environment with a comprehensive benchmark and accessible, extensible training resources, MedAgentGym delivers an integrated platform to develop LLM-based coding assistants for advanced biomedical data science.

CVMay 6, 2025Code
Novel Extraction of Discriminative Fine-Grained Feature to Improve Retinal Vessel Segmentation

Shuang Zeng, Chee Hong Lee, Micky C Nnamdi et al. · pku

Retinal vessel segmentation is a vital early detection method for several severe ocular diseases. Despite significant progress in retinal vessel segmentation with the advancement of Neural Networks, there are still challenges to overcome. Specifically, retinal vessel segmentation aims to predict the class label for every pixel within a fundus image, with a primary focus on intra-image discrimination, making it vital for models to extract more discriminative features. Nevertheless, existing methods primarily focus on minimizing the difference between the output from the decoder and the label, but ignore fully using feature-level fine-grained representations from the encoder. To address these issues, we propose a novel Attention U-shaped Kolmogorov-Arnold Network named AttUKAN along with a novel Label-guided Pixel-wise Contrastive Loss for retinal vessel segmentation. Specifically, we implement Attention Gates into Kolmogorov-Arnold Networks to enhance model sensitivity by suppressing irrelevant feature activations and model interpretability by non-linear modeling of KAN blocks. Additionally, we also design a novel Label-guided Pixel-wise Contrastive Loss to supervise our proposed AttUKAN to extract more discriminative features by distinguishing between foreground vessel-pixel pairs and background pairs. Experiments are conducted across four public datasets including DRIVE, STARE, CHASE_DB1, HRF and our private dataset. AttUKAN achieves F1 scores of 82.50%, 81.14%, 81.34%, 80.21% and 80.09%, along with MIoU scores of 70.24%, 68.64%, 68.59%, 67.21% and 66.94% in the above datasets, which are the highest compared to 11 networks for retinal vessel segmentation. Quantitative and qualitative results show that our AttUKAN achieves state-of-the-art performance and outperforms existing retinal vessel segmentation methods. Our code will be available at https://github.com/stevezs315/AttUKAN.

CLJan 13, 2024
EHRAgent: Code Empowers Large Language Models for Few-shot Complex Tabular Reasoning on Electronic Health Records

Wenqi Shi, Ran Xu, Yuchen Zhuang et al. · gatech

Large language models (LLMs) have demonstrated exceptional capabilities in planning and tool utilization as autonomous agents, but few have been developed for medical problem-solving. We propose EHRAgent, an LLM agent empowered with a code interface, to autonomously generate and execute code for multi-tabular reasoning within electronic health records (EHRs). First, we formulate an EHR question-answering task into a tool-use planning process, efficiently decomposing a complicated task into a sequence of manageable actions. By integrating interactive coding and execution feedback, EHRAgent learns from error messages and improves the originally generated code through iterations. Furthermore, we enhance the LLM agent by incorporating long-term memory, which allows EHRAgent to effectively select and build upon the most relevant successful cases from past experiences. Experiments on three real-world multi-tabular EHR datasets show that EHRAgent outperforms the strongest baseline by up to 29.6% in success rate. EHRAgent leverages the emerging few-shot learning capabilities of LLMs, enabling autonomous code generation and execution to tackle complex clinical tasks with minimal demonstrations.

CLMay 5, 2024
MedAdapter: Efficient Test-Time Adaptation of Large Language Models towards Medical Reasoning

Wenqi Shi, Ran Xu, Yuchen Zhuang et al. · gatech

Despite their improved capabilities in generation and reasoning, adapting large language models (LLMs) to the biomedical domain remains challenging due to their immense size and corporate privacy. In this work, we propose MedAdapter, a unified post-hoc adapter for test-time adaptation of LLMs towards biomedical applications. Instead of fine-tuning the entire LLM, MedAdapter effectively adapts the original model by fine-tuning only a small BERT-sized adapter to rank candidate solutions generated by LLMs. Experiments demonstrate that MedAdapter effectively adapts both white-box and black-box LLMs in biomedical reasoning, achieving average performance improvements of 25.48% and 11.31%, respectively, without requiring extensive computational resources or sharing data with third parties. MedAdapter also yields superior performance when combined with train-time adaptation, highlighting a flexible and complementary solution to existing adaptation methods. Faced with the challenges of balancing model performance, computational resources, and data privacy, MedAdapter provides an efficient, privacy-preserving, cost-effective, and transparent solution for adapting LLMs to the biomedical domain.

CYMar 20, 2025
Advancing Problem-Based Learning in Biomedical Engineering in the Era of Generative AI

Micky C. Nnamdi, J. Ben Tamo, Wenqi Shi et al.

Problem-Based Learning (PBL) has significantly impacted biomedical engineering (BME) education since its introduction in the early 2000s, effectively enhancing critical thinking and real-world knowledge application among students. With biomedical engineering rapidly converging with artificial intelligence (AI), integrating effective AI education into established curricula has become challenging yet increasingly necessary. Recent advancements, including AI's recognition by the 2024 Nobel Prize, have highlighted the importance of training students comprehensively in biomedical AI. However, effective biomedical AI education faces substantial obstacles, such as diverse student backgrounds, limited personalized mentoring, constrained computational resources, and difficulties in safely scaling hands-on practical experiments due to privacy and ethical concerns associated with biomedical data. To overcome these issues, we conducted a three-year (2021-2023) case study implementing an advanced PBL framework tailored specifically for biomedical AI education, involving 92 undergraduate and 156 graduate students from the joint Biomedical Engineering program of Georgia Institute of Technology and Emory University. Our approach emphasizes collaborative, interdisciplinary problem-solving through authentic biomedical AI challenges. The implementation led to measurable improvements in learning outcomes, evidenced by high research productivity (16 student-authored publications), consistently positive peer evaluations, and successful development of innovative computational methods addressing real biomedical challenges. Additionally, we examined the role of generative AI both as a teaching subject and an educational support tool within the PBL framework. Our study presents a practical and scalable roadmap for biomedical engineering departments aiming to integrate robust AI education into their curricula.

CLJan 19
LLM-as-RNN: A Recurrent Language Model for Memory Updates and Sequence Prediction

Yuxing Lu, J. Ben Tamo, Weichen Zhao et al.

Large language models are strong sequence predictors, yet standard inference relies on immutable context histories. After making an error at generation step t, the model lacks an updatable memory mechanism that improves predictions for step t+1. We propose LLM-as-RNN, an inference-only framework that turns a frozen LLM into a recurrent predictor by representing its hidden state as natural-language memory. This state, implemented as a structured system-prompt summary, is updated at each timestep via feedback-driven text rewrites, enabling learning without parameter updates. Under a fixed token budget, LLM-as-RNN corrects errors and retains task-relevant patterns, effectively performing online learning through language. We evaluate the method on three sequential benchmarks in healthcare, meteorology, and finance across Llama, Gemma, and GPT model families. LLM-as-RNN significantly outperforms zero-shot, full-history, and MemPrompt baselines, improving predictive accuracy by 6.5% on average, while producing interpretable, human-readable learning traces absent in standard context accumulation.

HCDec 5, 2025
EXR: An Interactive Immersive EHR Visualization in Extended Reality

Benoit Marteau, Shaun Q. Y. Tan, Jieru Li et al.

This paper presents the design and implementation of an Extended Reality (XR) platform for immersive, interactive visualization of Electronic Health Records (EHRs). The system extends beyond conventional 2D interfaces by visualizing both structured and unstructured patient data into a shared 3D environment, enabling intuitive exploration and real-time collaboration. The modular infrastructure integrates FHIR-based EHR data with volumetric medical imaging and AI-generated segmentation, ensuring interoperability with modern healthcare systems. The platform's capabilities are demonstrated using synthetic EHR datasets and computed tomography (CT)-derived spine models processed through an AI-powered segmentation pipeline. This work suggests that such integrated XR solutions could form the foundation for next-generation clinical decision-support tools, where advanced data infrastructures are directly accessible in an interactive and spatially rich environment.

AINov 22, 2025
Leveraging Evidence-Guided LLMs to Enhance Trustworthy Depression Diagnosis

Yining Yuan, J. Ben Tamo, Micky C. Nnamdi et al.

Large language models (LLMs) show promise in automating clinical diagnosis, yet their non-transparent decision-making and limited alignment with diagnostic standards hinder trust and clinical adoption. We address this challenge by proposing a two-stage diagnostic framework that enhances transparency, trustworthiness, and reliability. First, we introduce Evidence-Guided Diagnostic Reasoning (EGDR), which guides LLMs to generate structured diagnostic hypotheses by interleaving evidence extraction with logical reasoning grounded in DSM-5 criteria. Second, we propose a Diagnosis Confidence Scoring (DCS) module that evaluates the factual accuracy and logical consistency of generated diagnoses through two interpretable metrics: the Knowledge Attribution Score (KAS) and the Logic Consistency Score (LCS). Evaluated on the D4 dataset with pseudo-labels, EGDR outperforms direct in-context prompting and Chain-of-Thought (CoT) across five LLMs. For instance, on OpenBioLLM, EGDR improves accuracy from 0.31 (Direct) to 0.76 and increases DCS from 0.50 to 0.67. On MedLlama, DCS rises from 0.58 (CoT) to 0.77. Overall, EGDR yields up to +45% accuracy and +36% DCS gains over baseline methods, offering a clinically grounded, interpretable foundation for trustworthy AI-assisted diagnosis.

CLOct 16, 2025
MetaBench: A Multi-task Benchmark for Assessing LLMs in Metabolomics

Yuxing Lu, Xukai Zhao, J. Ben Tamo et al. · pku

Large Language Models (LLMs) have demonstrated remarkable capabilities on general text; however, their proficiency in specialized scientific domains that require deep, interconnected knowledge remains largely uncharacterized. Metabolomics presents unique challenges with its complex biochemical pathways, heterogeneous identifier systems, and fragmented databases. To systematically evaluate LLM capabilities in this domain, we introduce MetaBench, the first benchmark for metabolomics assessment. Curated from authoritative public resources, MetaBench evaluates five capabilities essential for metabolomics research: knowledge, understanding, grounding, reasoning, and research. Our evaluation of 25 open- and closed-source LLMs reveals distinct performance patterns across metabolomics tasks: while models perform well on text generation tasks, cross-database identifier grounding remains challenging even with retrieval augmentation. Model performance also decreases on long-tail metabolites with sparse annotations. With MetaBench, we provide essential infrastructure for developing and evaluating metabolomics AI systems, enabling systematic progress toward reliable computational tools for metabolomics research.

AIDec 23, 2021
Explainable Artificial Intelligence Methods in Combating Pandemics: A Systematic Review

Felipe Giuste, Wenqi Shi, Yuanda Zhu et al.

Despite the myriad peer-reviewed papers demonstrating novel Artificial Intelligence (AI)-based solutions to COVID-19 challenges during the pandemic, few have made significant clinical impact. The impact of artificial intelligence during the COVID-19 pandemic was greatly limited by lack of model transparency. This systematic review examines the use of Explainable Artificial Intelligence (XAI) during the pandemic and how its use could overcome barriers to real-world success. We find that successful use of XAI can improve model performance, instill trust in the end-user, and provide the value needed to affect user decision-making. We introduce the reader to common XAI techniques, their utility, and specific examples of their application. Evaluation of XAI results is also discussed as an important step to maximize the value of AI-based clinical decision support systems. We illustrate the classical, modern, and potential future trends of XAI to elucidate the evolution of novel XAI techniques. Finally, we provide a checklist of suggestions during the experimental design process supported by recent publications. Common challenges during the implementation of AI solutions are also addressed with specific examples of potential solutions. We hope this review may serve as a guide to improve the clinical impact of future AI-based solutions.

LGSep 22, 2020
Public Health Informatics: Proposing Causal Sequence of Death Using Neural Machine Translation

Yuanda Zhu, Ying Sha, Hang Wu et al.

Each year there are nearly 57 million deaths around the world, with over 2.7 million in the United States. Timely, accurate and complete death reporting is critical in public health, as institutions and government agencies rely on death reports to analyze vital statistics and to formulate responses to communicable diseases. Inaccurate death reporting may result in potential misdirection of public health policies. Determining the causes of death is, nevertheless, challenging even for experienced physicians. To facilitate physicians in accurately reporting causes of death, we present an advanced AI approach to determine a chronically ordered sequence of clinical conditions that lead to death, based on decedent's last hospital discharge record. The sequence of clinical codes on the death report is named as causal chain of death, coded in the tenth revision of International Statistical Classification of Diseases (ICD-10); in line with the ICD-9-CM Official Guidelines for Coding and Reporting, the priority-ordered clinical conditions on the discharge record are coded in ICD-9. We identify three challenges in proposing the causal chain of death: two versions of coding system in clinical codes, medical domain knowledge conflict, and data interoperability. To overcome the first challenge in this sequence-to-sequence problem, we apply neural machine translation models to generate target sequence. Along with three accuracy metrics, we evaluate the quality of generated sequences with the BLEU (BiLingual Evaluation Understudy) score and achieve 16.04 out of 100. To address the second challenge, we incorporate expert-verified medical domain knowledge as constraint in generating output sequence to exclude infeasible causal chains. Lastly, we demonstrate the usability of our work in a Fast Healthcare Interoperability Resources (FHIR) interface to address the third challenge.

CLMay 6, 2017
DeepDeath: Learning to Predict the Underlying Cause of Death with Big Data

Hamid Reza Hassanzadeh, Ying Sha, May D. Wang

Multiple cause-of-death data provides a valuable source of information that can be used to enhance health standards by predicting health related trajectories in societies with large populations. These data are often available in large quantities across U.S. states and require Big Data techniques to uncover complex hidden patterns. We design two different classes of models suitable for large-scale analysis of mortality data, a Hadoop-based ensemble of random forests trained over N-grams, and the DeepDeath, a deep classifier based on the recurrent neural network (RNN). We apply both classes to the mortality data provided by the National Center for Health Statistics and show that while both perform significantly better than the random classifier, the deep model that utilizes long short-term memory networks (LSTMs), surpasses the N-gram based models and is capable of learning the temporal aspect of the data without a need for building ad-hoc, expert-driven features.

QMMay 4, 2017
MotifMark: Finding Regulatory Motifs in DNA Sequences

Hamid Reza Hassanzadeh, Pushkar Kolhe, Charles L. Isbell et al.

The interaction between proteins and DNA is a key driving force in a significant number of biological processes such as transcriptional regulation, repair, recombination, splicing, and DNA modification. The identification of DNA-binding sites and the specificity of target proteins in binding to these regions are two important steps in understanding the mechanisms of these biological activities. A number of high-throughput technologies have recently emerged that try to quantify the affinity between proteins and DNA motifs. Despite their success, these technologies have their own limitations and fall short in precise characterization of motifs, and as a result, require further downstream analysis to extract useful and interpretable information from a haystack of noisy and inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory and machine learning, that can find binding sites on candidate probes and rank their specificity in regard to the underlying transcription factor. We developed a pipeline to analyze experimental data derived from compact universal protein binding microarrays and benchmarked it against two of the most accurate motif search methods. Our results indicate that MotifMark can be a viable alternative technique for prediction of motif from protein binding microarrays and possibly other related high-throughput techniques.

CVNov 17, 2016
DeeperBind: Enhancing Prediction of Sequence Specificities of DNA Binding Proteins

Hamid Reza Hassanzadeh, May D. Wang

Transcription factors (TFs) are macromolecules that bind to \textit{cis}-regulatory specific sub-regions of DNA promoters and initiate transcription. Finding the exact location of these binding sites (aka motifs) is important in a variety of domains such as drug design and development. To address this need, several \textit{in vivo} and \textit{in vitro} techniques have been developed so far that try to characterize and predict the binding specificity of a protein to different DNA loci. The major problem with these techniques is that they are not accurate enough in prediction of the binding affinity and characterization of the corresponding motifs. As a result, downstream analysis is required to uncover the locations where proteins of interest bind. Here, we propose DeeperBind, a long short term recurrent convolutional network for prediction of protein binding specificities with respect to DNA probes. DeeperBind can model the positional dynamics of probe sequences and hence reckons with the contributions made by individual sub-regions in DNA sequences, in an effective way. Moreover, it can be trained and tested on datasets containing varying-length sequences. We apply our pipeline to the datasets derived from protein binding microarrays (PBMs), an in-vitro high-throughput technology for quantification of protein-DNA binding preferences, and present promising results. To the best of our knowledge, this is the most accurate pipeline that can predict binding specificities of DNA sequences from the data produced by high-throughput technologies through utilization of the power of deep learning for feature generation and positional dynamics modeling.

LGNov 17, 2016
A Multi-Modal Graph-Based Semi-Supervised Pipeline for Predicting Cancer Survival

Hamid Reza Hassanzadeh, John H. Phan, May D. Wang

Cancer survival prediction is an active area of research that can help prevent unnecessary therapies and improve patient's quality of life. Gene expression profiling is being widely used in cancer studies to discover informative biomarkers that aid predict different clinical endpoint prediction. We use multiple modalities of data derived from RNA deep-sequencing (RNA-seq) to predict survival of cancer patients. Despite the wealth of information available in expression profiles of cancer tumors, fulfilling the aforementioned objective remains a big challenge, for the most part, due to the paucity of data samples compared to the high dimension of the expression profiles. As such, analysis of transcriptomic data modalities calls for state-of-the-art big-data analytics techniques that can maximally use all the available data to discover the relevant information hidden within a significant amount of noise. In this paper, we propose a pipeline that predicts cancer patients' survival by exploiting the structure of the input (manifold learning) and by leveraging the unlabeled samples using Laplacian support vector machines, a graph-based semi supervised learning (GSSL) paradigm. We show that under certain circumstances, no single modality per se will result in the best accuracy and by fusing different models together via a stacked generalization strategy, we may boost the accuracy synergistically. We apply our approach to two cancer datasets and present promising results. We maintain that a similar pipeline can be used for predictive tasks where labeled samples are expensive to acquire.

LGSep 29, 2015
A Semi-Supervised Method for Predicting Cancer Survival Using Incomplete Clinical Data

Hamid Reza Hassanzadeh, John H. Phan, May D. Wang

Prediction of survival for cancer patients is an open area of research. However, many of these studies focus on datasets with a large number of patients. We present a novel method that is specifically designed to address the challenge of data scarcity, which is often the case for cancer datasets. Our method is able to use unlabeled data to improve classification by adopting a semi-supervised training approach to learn an ensemble classifier. The results of applying our method to three cancer datasets show the promise of semi-supervised learning for prediction of cancer survival.