Jack Lanchantin

LG
h-index34
28papers
3,281citations
Novelty53%
AI Score58

28 Papers

LGSep 14, 2023Code
A Data Source for Reasoning Embodied Agents

Jack Lanchantin, Sainbayar Sukhbaatar, Gabriel Synnaeve et al. · meta-ai

Recent progress in using machine learning models for reasoning tasks has been driven by novel model architectures, large-scale pre-training protocols, and dedicated reasoning datasets for fine-tuning. In this work, to further pursue these advances, we introduce a new data generator for machine reasoning that integrates with an embodied agent. The generated data consists of templated text queries and answers, matched with world-states encoded into a database. The world-states are a result of both world dynamics and the actions of the agent. We show the results of several baseline models on instantiations of train sets. These include pre-trained language models fine-tuned on a text-formatted representation of the database, and graph-structured Transformers operating on a knowledge-graph representation of the database. We find that these models can answer some questions about the world-state, but struggle with others. These results hint at new research directions in designing neural reasoning models and database representations. Code to generate the data will be released at github.com/facebookresearch/neuralmemory

98.6AIMar 19
Reasoning over mathematical objects: on-policy reward modeling and test time aggregation

Pranjal Aggarwal, Marjan Ghazvininejad, Seungone Kim et al. · meta-ai

The ability to precisely derive mathematical objects is a core requirement for downstream STEM applications, including mathematics, physics, and chemistry, where reasoning must culminate in formally structured expressions. Yet, current LM evaluations of mathematical and scientific reasoning rely heavily on simplified answer formats such as numerical values or multiple choice options due to the convenience of automated assessment. In this paper we provide three contributions for improving reasoning over mathematical objects: (i) we build and release training data and benchmarks for deriving mathematical objects, the Principia suite; (ii) we provide training recipes with strong LLM-judges and verifiers, where we show that on-policy judge training boosts performance; (iii) we show how on-policy training can also be used to scale test-time compute via aggregation. We find that strong LMs such as Qwen3-235B and o3 struggle on Principia, while our training recipes can bring significant improvements over different LLM backbones, while simultaneously improving results on existing numerical and MCQA tasks, demonstrating cross-format generalization of reasoning abilities.

LGApr 17, 2019Code
Neural Message Passing for Multi-Label Classification

Jack Lanchantin, Arshdeep Sekhon, Yanjun Qi

Multi-label classification (MLC) is the task of assigning a set of target labels for a given sample. Modeling the combinatorial label interactions in MLC has been a long-haul challenge. We propose Label Message Passing (LaMP) Neural Networks to efficiently model the joint prediction of multiple labels. LaMP treats labels as nodes on a label-interaction graph and computes the hidden representation of each label node conditioned on the input using attention-based neural message passing. Attention enables LaMP to assign different importance to neighbor nodes per label, learning how labels interact (implicitly). The proposed models are simple, accurate, interpretable, structure-agnostic, and applicable for predicting dense labels since LaMP is incredibly parallelizable. We validate the benefits of LaMP on seven real-world MLC datasets, covering a broad spectrum of input/output types and outperforming the state-of-the-art results. Notably, LaMP enables intuitive interpretation of how classifying each label depends on the elements of a sample and at the same time rely on its interaction with other labels. We provide our code and datasets at https://github.com/QData/LaMP

LGApr 24, 2017Code
GaKCo: a Fast GApped k-mer string Kernel using COunting

Ritambhara Singh, Arshdeep Sekhon, Kamran Kowsari et al.

String Kernel (SK) techniques, especially those using gapped $k$-mers as features (gk), have obtained great success in classifying sequences like DNA, protein, and text. However, the state-of-the-art gk-SK runs extremely slow when we increase the dictionary size ($Σ$) or allow more mismatches ($M$). This is because current gk-SK uses a trie-based algorithm to calculate co-occurrence of mismatched substrings resulting in a time cost proportional to $O(Σ^{M})$. We propose a \textbf{fast} algorithm for calculating \underline{Ga}pped $k$-mer \underline{K}ernel using \underline{Co}unting (GaKCo). GaKCo uses associative arrays to calculate the co-occurrence of substrings using cumulative counting. This algorithm is fast, scalable to larger $Σ$ and $M$, and naturally parallelizable. We provide a rigorous asymptotic analysis that compares GaKCo with the state-of-the-art gk-SK. Theoretically, the time cost of GaKCo is independent of the $Σ^{M}$ term that slows down the trie-based approach. Experimentally, we observe that GaKCo achieves the same accuracy as the state-of-the-art and outperforms its speed by factors of 2, 100, and 4, on classifying sequences of DNA (5 datasets), protein (12 datasets), and character-based English text (2 datasets), respectively. GaKCo is shared as an open source tool at \url{https://github.com/QData/GaKCo-SVM}

CLJan 30, 2025
Diverse Preference Optimization

Jack Lanchantin, Angelica Chen, Shehzaad Dhuliawala et al. · meta-ai

Post-training of language models, either through reinforcement learning, preference optimization or supervised finetuning, tends to sharpen the output probability distribution and reduce the diversity of generated responses. This is particularly a problem for creative generative tasks where varied responses are desired. In this work we introduce Diverse Preference Optimization (DivPO), an optimization method which learns to generate much more diverse responses than standard pipelines, while maintaining the quality of the generations. In DivPO, preference pairs are selected by first considering a pool of responses, and a measure of diversity among them, and selecting chosen examples as being more rare but high quality, while rejected examples are more common, but low quality. DivPO results in generating 45.6% more diverse persona attributes, and a 74.6% increase in story diversity, while maintaining similar win rates as standard baselines. On general instruction following, DivPO results in a 46.2% increase in diversity, and a 2.4% winrate improvement compared to DPO.

CLFeb 21, 2024
TOOLVERIFIER: Generalization to New Tools via Self-Verification

Dheeraj Mekala, Jason Weston, Jack Lanchantin et al. · meta-ai

Teaching language models to use tools is an important milestone towards building general assistants, but remains an open problem. While there has been significant progress on learning to use specific tools via fine-tuning, language models still struggle with learning how to robustly use new tools from only a few demonstrations. In this work we introduce a self-verification method which distinguishes between close candidates by self-asking contrastive questions during (1) tool selection; and (2) parameter generation. We construct synthetic, high-quality, self-generated data for this goal using Llama-2 70B, which we intend to release publicly. Extensive experiments on 4 tasks from the ToolBench benchmark, consisting of 17 unseen tools, demonstrate an average improvement of 22% over few-shot baselines, even in scenarios where the distinctions between candidate tools are finely nuanced.

LGFeb 12, 2025
LLM Pretraining with Continuous Concepts

Jihoon Tack, Jack Lanchantin, Jane Yu et al. · meta-ai

Next token prediction has been the standard training objective used in large language model pretraining. Representations are learned as a result of optimizing for token-level perplexity. We propose Continuous Concept Mixing (CoCoMix), a novel pretraining framework that combines discrete next token prediction with continuous concepts. Specifically, CoCoMix predicts continuous concepts learned from a pretrained sparse autoencoder and mixes them into the model's hidden state by interleaving with token hidden representations. Through experiments on multiple benchmarks, including language modeling and downstream reasoning tasks, we show that CoCoMix is more sample efficient and consistently outperforms standard next token prediction, knowledge distillation and inserting pause tokens. We find that combining both concept learning and interleaving in an end-to-end framework is critical to performance gains. Furthermore, CoCoMix enhances interpretability and steerability by allowing direct inspection and modification of the predicted concept, offering a transparent way to guide the model's internal reasoning process.

CLSep 2, 2025
Jointly Reinforcing Diversity and Quality in Language Model Generations

Tianjian Li, Yiming Zhang, Ping Yu et al. · meta-ai

Post-training of Large Language Models (LMs) often prioritizes accuracy and helpfulness at the expense of diversity. This creates a tension: while post-training improves response quality, it also sharpens output distributions and reduces the range of ideas, limiting the usefulness of LMs in creative and exploratory tasks such as brainstorming, storytelling, or problem solving. We address this challenge with Diversity-Aware Reinforcement Learning (DARLING), a framework that jointly optimizes for response quality and semantic diversity. At its core, DARLING introduces a learned partition function to measure diversity beyond surface-level lexical variations. This diversity signal is then combined with a quality reward during online reinforcement learning, encouraging models to generate outputs that are both high-quality and distinct. Experiments across multiple model families and sizes show that DARLING generalizes to two regimes: non-verifiable tasks (instruction following and creative writing) and verifiable tasks (competition math). On five benchmarks in the first setting, DARLING consistently outperforms quality-only RL baselines, producing outputs that are simultaneously of higher quality and novelty. In the second setting, DARLING achieves higher pass@1 (solution quality) and pass@k (solution variety). Most strikingly, explicitly optimizing for diversity catalyzes exploration in online RL, which manifests itself as higher-quality responses.

CLJun 26, 2025
Bridging Offline and Online Reinforcement Learning for LLMs

Jack Lanchantin, Angelica Chen, Janice Lan et al. · meta-ai

We investigate the effectiveness of reinforcement learning methods for finetuning large language models when transitioning from offline to semi-online to fully online regimes for both verifiable and non-verifiable tasks. Our experiments cover training on verifiable math as well as non-verifiable instruction following with a set of benchmark evaluations for both. Across these settings, we extensively compare online and semi-online Direct Preference Optimization and Group Reward Policy Optimization objectives, and surprisingly find similar performance and convergence between these variants, which all strongly outperform offline methods. We provide a detailed analysis of the training dynamics and hyperparameter selection strategies to achieve optimal results. Finally, we show that multi-tasking with verifiable and non-verifiable rewards jointly yields improved performance across both task types.

CLNov 14, 2024
Adaptive Decoding via Latent Preference Optimization

Shehzaad Dhuliawala, Ilia Kulikov, Ping Yu et al. · meta-ai

During language model decoding, it is known that using higher temperature sampling gives more creative responses, while lower temperatures are more factually accurate. However, such models are commonly applied to general instruction following, which involves both creative and fact seeking tasks, using a single fixed temperature across all examples and tokens. In this work, we introduce Adaptive Decoding, a layer added to the model to select the sampling temperature dynamically at inference time, at either the token or example level, in order to optimize performance. To learn its parameters we introduce Latent Preference Optimization (LPO) a general approach to train discrete latent variables such as choices of temperature. Our method outperforms all fixed decoding temperatures across a range of tasks that require different temperatures, including UltraFeedback, Creative Story Writing, and GSM8K.

CLAug 18, 2025
OptimalThinkingBench: Evaluating Over and Underthinking in LLMs

Pranjal Aggarwal, Seungone Kim, Jack Lanchantin et al. · cmu, meta-ai

Thinking LLMs solve complex tasks at the expense of increased compute and overthinking on simpler problems, while non-thinking LLMs are faster and cheaper but underthink on harder reasoning problems. This has led to the development of separate thinking and non-thinking LLM variants, leaving the onus of selecting the optimal model for each query on the end user. We introduce OptimalThinkingBench, a unified benchmark that jointly evaluates overthinking and underthinking in LLMs and also encourages the development of optimally-thinking models that balance performance and efficiency. Our benchmark comprises two sub-benchmarks: OverthinkingBench, featuring simple math and general queries in 72 domains, and UnderthinkingBench, containing 11 challenging reasoning tasks along with harder math problems. Using novel thinking-adjusted accuracy metrics, we extensively evaluate 33 different thinking and non-thinking models and show that no model is able to optimally think on our benchmark. Thinking models often overthink for hundreds of tokens on the simplest user queries without improving performance. In contrast, large non-thinking models underthink, often falling short of much smaller thinking models. We further explore several methods to encourage optimal thinking, but find that these approaches often improve on one sub-benchmark at the expense of the other, highlighting the need for better unified and optimal models in the future.

AIJul 31, 2025
CoT-Self-Instruct: Building high-quality synthetic prompts for reasoning and non-reasoning tasks

Ping Yu, Jack Lanchantin, Tianlu Wang et al. · meta-ai

We propose CoT-Self-Instruct, a synthetic data generation method that instructs LLMs to first reason and plan via Chain-of-Thought (CoT) based on given seed tasks, and then generate a new synthetic example of similar quality and complexity. This is followed by a filtering step to select high-quality data using automatic metrics, which are then used for LLM training. In verifiable reasoning, our synthetic data significantly outperforms existing training datasets, such as s1k and OpenMathReasoning, when evaluated on MATH500, AMC23, AIME24, and GPQA-Diamond. For non-verifiable instruction-following tasks, our method surpasses the performance of both human and standard Self-Instruct training data on the AlpacaEval 2.0 and Arena-Hard benchmarks.

CLJul 2, 2025
NaturalThoughts: Selecting and Distilling Reasoning Traces for General Reasoning Tasks

Yang Li, Youssef Emad, Karthik Padthe et al. · meta-ai

Recent work has shown that distilling reasoning traces from a larger teacher model via supervised finetuning outperforms reinforcement learning with the smaller student model alone (Guo et al. 2025). However, there has not been a systematic study of what kind of reasoning demonstrations from the teacher are most effective in improving the student model's reasoning capabilities. In this work we curate high-quality "NaturalThoughts" by selecting reasoning traces from a strong teacher model based on a large pool of questions from NaturalReasoning (Yuan et al. 2025). We first conduct a systematic analysis of factors that affect distilling reasoning capabilities, in terms of sample efficiency and scalability for general reasoning tasks. We observe that simply scaling up data size with random sampling is a strong baseline with steady performance gains. Further, we find that selecting difficult examples that require more diverse reasoning strategies is more sample-efficient to transfer the teacher model's reasoning skills. Evaluated on both Llama and Qwen models, training with NaturalThoughts outperforms existing reasoning datasets such as OpenThoughts, LIMO, etc. on general STEM reasoning benchmarks including GPQA-Diamond, MMLU-Pro and SuperGPQA.

CLOct 28, 2025
SPICE: Self-Play In Corpus Environments Improves Reasoning

Bo Liu, Chuanyang Jin, Seungone Kim et al. · meta-ai

Self-improving systems require environmental interaction for continuous adaptation. We introduce SPICE (Self-Play In Corpus Environments), a reinforcement learning framework where a single model acts in two roles: a Challenger that mines documents from a large corpus to generate diverse reasoning tasks, and a Reasoner that solves them. Through adversarial dynamics, the Challenger creates an automatic curriculum at the frontier of the Reasoner's capability, while corpus grounding provides the rich, near-inexhaustible external signal necessary for sustained improvement. Unlike existing ungrounded self-play methods that offer more limited benefits, SPICE achieves consistent gains across mathematical (+8.9%) and general reasoning (+9.8%) benchmarks on multiple model families. Our analysis reveals how document grounding is a key ingredient in SPICE to continuously generate its own increasingly challenging goals and achieve them, enabling sustained self-improvement.

CLSep 25, 2025
LLM Output Homogenization is Task Dependent

Shomik Jain, Jack Lanchantin, Maximilian Nickel et al. · meta-ai

A large language model can be less helpful if it exhibits output response homogenization. But whether two responses are considered homogeneous, and whether such homogenization is problematic, both depend on the task category. For instance, in objective math tasks, we often expect no variation in the final answer but anticipate variation in the problem-solving strategy. Whereas, for creative writing tasks, we may expect variation in key narrative components (e.g. plot, genre, setting, etc), beyond the vocabulary or embedding diversity produced by temperature-sampling. Previous work addressing output homogenization often fails to conceptualize diversity in a task-dependent way. We address this gap in the literature directly by making the following contributions. (1) We present a task taxonomy comprised of eight task categories that each have distinct conceptualizations of output homogenization. (2) We introduce task-anchored functional diversity to better evaluate output homogenization. (3) We propose a task-anchored sampling technique that increases functional diversity for task categories where homogenization is undesired, while preserving homogenization where it is desired. (4) We challenge the perceived existence of a diversity-quality trade-off by increasing functional diversity while maintaining response quality. Overall, we demonstrate how task dependence improves the evaluation and mitigation of output homogenization.

LGMay 1, 2023
Learning to Reason and Memorize with Self-Notes

Jack Lanchantin, Shubham Toshniwal, Jason Weston et al.

Large language models have been shown to struggle with multi-step reasoning, and do not retain previous reasoning steps for future use. We propose a simple method for solving both of these problems by allowing the model to take Self-Notes. Unlike recent chain-of-thought or scratchpad approaches, the model can deviate from the input context at any time to explicitly think and write down its thoughts. This allows the model to perform reasoning on the fly as it reads the context and even integrate previous reasoning steps, thus enhancing its memory with useful information and enabling multi-step reasoning. Experiments across a wide variety of tasks demonstrate that our method can outperform chain-of-thought and scratchpad methods by taking Self-Notes that interleave the input text.

CVNov 27, 2020
General Multi-label Image Classification with Transformers

Jack Lanchantin, Tianlu Wang, Vicente Ordonez et al.

Multi-label image classification is the task of predicting a set of labels corresponding to objects, attributes or other entities present in an image. In this work we propose the Classification Transformer (C-Tran), a general framework for multi-label image classification that leverages Transformers to exploit the complex dependencies among visual features and labels. Our approach consists of a Transformer encoder trained to predict a set of target labels given an input set of masked labels, and visual features from a convolutional neural network. A key ingredient of our method is a label mask training objective that uses a ternary encoding scheme to represent the state of the labels as positive, negative, or unknown during training. Our model shows state-of-the-art performance on challenging datasets such as COCO and Visual Genome. Moreover, because our model explicitly represents the uncertainty of labels during training, it is more general by allowing us to produce improved results for images with partial or extra label annotations during inference. We demonstrate this additional capability in the COCO, Visual Genome, News500, and CUB image datasets.

CLApr 25, 2020
Reevaluating Adversarial Examples in Natural Language

John X. Morris, Eli Lifland, Jack Lanchantin et al.

State-of-the-art attacks on NLP models lack a shared definition of a what constitutes a successful attack. We distill ideas from past work into a unified framework: a successful natural language adversarial example is a perturbation that fools the model and follows some linguistic constraints. We then analyze the outputs of two state-of-the-art synonym substitution attacks. We find that their perturbations often do not preserve semantics, and 38% introduce grammatical errors. Human surveys reveal that to successfully preserve semantics, we need to significantly increase the minimum cosine similarities between the embeddings of swapped words and between the sentence encodings of original and perturbed sentences.With constraints adjusted to better preserve semantics and grammaticality, the attack success rate drops by over 70 percentage points.

SEMar 21, 2018
Exploring the Naturalness of Buggy Code with Recurrent Neural Networks

Jack Lanchantin, Ji Gao

Statistical language models are powerful tools which have been used for many tasks within natural language processing. Recently, they have been used for other sequential data such as source code.(Ray et al., 2015) showed that it is possible train an n-gram source code language mode, and use it to predict buggy lines in code by determining "unnatural" lines via entropy with respect to the language model. In this work, we propose using a more advanced language modeling technique, Long Short-term Memory recurrent neural networks, to model source code and classify buggy lines based on entropy. We show that our method slightly outperforms an n-gram model in the buggy line classification task using AUC.

CLJan 13, 2018
Black-box Generation of Adversarial Text Sequences to Evade Deep Learning Classifiers

Ji Gao, Jack Lanchantin, Mary Lou Soffa et al.

Although various techniques have been proposed to generate adversarial samples for white-box attacks on text, little attention has been paid to black-box attacks, which are more realistic scenarios. In this paper, we present a novel algorithm, DeepWordBug, to effectively generate small text perturbations in a black-box setting that forces a deep-learning classifier to misclassify a text input. We employ novel scoring strategies to identify the critical tokens that, if modified, cause the classifier to make an incorrect prediction. Simple character-level transformations are applied to the highest-ranked tokens in order to minimize the edit distance of the perturbation, yet change the original classification. We evaluated DeepWordBug on eight real-world text datasets, including text classification, sentiment analysis, and spam detection. We compare the result of DeepWordBug with two baselines: Random (Black-box) and Gradient (White-box). Our experimental results indicate that DeepWordBug reduces the prediction accuracy of current state-of-the-art deep-learning models, including a decrease of 68\% on average for a Word-LSTM model and 48\% on average for a Char-CNN model.

LGOct 30, 2017
Prototype Matching Networks for Large-Scale Multi-label Genomic Sequence Classification

Jack Lanchantin, Arshdeep Sekhon, Ritambhara Singh et al.

One of the fundamental tasks in understanding genomics is the problem of predicting Transcription Factor Binding Sites (TFBSs). With more than hundreds of Transcription Factors (TFs) as labels, genomic-sequence based TFBS prediction is a challenging multi-label classification task. There are two major biological mechanisms for TF binding: (1) sequence-specific binding patterns on genomes known as "motifs" and (2) interactions among TFs known as co-binding effects. In this paper, we propose a novel deep architecture, the Prototype Matching Network (PMN) to mimic the TF binding mechanisms. Our PMN model automatically extracts prototypes ("motif"-like features) for each TF through a novel prototype-matching loss. Borrowing ideas from few-shot matching models, we use the notion of support set of prototypes and an LSTM to learn how TFs interact and bind to genomic sequences. On a reference TFBS dataset with $2.1$ $million$ genomic sequences, PMN significantly outperforms baselines and validates our design choices empirically. To our knowledge, this is the first deep learning architecture that introduces prototype learning and considers TF-TF interactions for large-scale TFBS prediction. Not only is the proposed architecture accurate, but it also models the underlying biology.

LGAug 1, 2017
Attend and Predict: Understanding Gene Regulation by Selective Attention on Chromatin

Ritambhara Singh, Jack Lanchantin, Arshdeep Sekhon et al.

The past decade has seen a revolution in genomic technologies that enable a flood of genome-wide profiling of chromatin marks. Recent literature tried to understand gene regulation by predicting gene expression from large-scale chromatin measurements. Two fundamental challenges exist for such learning tasks: (1) genome-wide chromatin signals are spatially structured, high-dimensional and highly modular; and (2) the core aim is to understand what are the relevant factors and how they work together? Previous studies either failed to model complex dependencies among input signals or relied on separate feature analysis to explain the decisions. This paper presents an attention-based deep learning approach; we call AttentiveChrome, that uses a unified architecture to model and to interpret dependencies among chromatin factors for controlling gene regulation. AttentiveChrome uses a hierarchy of multiple Long short-term memory (LSTM) modules to encode the input signals and to model how various chromatin marks cooperate automatically. AttentiveChrome trains two levels of attention jointly with the target prediction, enabling it to attend differentially to relevant marks and to locate important positions per mark. We evaluate the model across 56 different cell types (tasks) in human. Not only is the proposed architecture more accurate, but its attention scores also provide a better interpretation than state-of-the-art feature visualization methods such as saliency map. Code and data are shared at www.deepchrome.org

LGFeb 22, 2017
Memory Matching Networks for Genomic Sequence Classification

Jack Lanchantin, Ritambhara Singh, Yanjun Qi

When analyzing the genome, researchers have discovered that proteins bind to DNA based on certain patterns of the DNA sequence known as "motifs". However, it is difficult to manually construct motifs due to their complexity. Recently, externally learned memory models have proven to be effective methods for reasoning over inputs and supporting sets. In this work, we present memory matching networks (MMN) for classifying DNA sequences as protein binding sites. Our model learns a memory bank of encoded motifs, which are dynamic memory modules, and then matches a new test sequence to each of the motifs to classify the sequence as a binding or nonbinding site.

LGSep 12, 2016
Transfer String Kernel for Cross-Context DNA-Protein Binding Prediction

Ritambhara Singh, Jack Lanchantin, Gabriel Robins et al.

Through sequence-based classification, this paper tries to accurately predict the DNA binding sites of transcription factors (TFs) in an unannotated cellular context. Related methods in the literature fail to perform such predictions accurately, since they do not consider sample distribution shift of sequence segments from an annotated (source) context to an unannotated (target) context. We, therefore, propose a method called "Transfer String Kernel" (TSK) that achieves improved prediction of transcription factor binding site (TFBS) using knowledge transfer via cross-context sample adaptation. TSK maps sequence segments to a high-dimensional feature space using a discriminative mismatch string kernel framework. In this high-dimensional space, labeled examples of the source context are re-weighted so that the revised sample distribution matches the target context more closely. We have experimentally verified TSK for TFBS identifications on fourteen different TFs under a cross-organism setting. We find that TSK consistently outperforms the state-of the-art TFBS tools, especially when working with TFs whose binding sequences are not conserved across contexts. We also demonstrate the generalizability of TSK by showing its cutting-edge performance on a different set of cross-context tasks for the MHC peptide binding predictions.

LGAug 12, 2016
Deep Motif Dashboard: Visualizing and Understanding Genomic Sequences Using Deep Neural Networks

Jack Lanchantin, Ritambhara Singh, Beilun Wang et al.

Deep neural network (DNN) models have recently obtained state-of-the-art prediction accuracy for the transcription factor binding (TFBS) site classification task. However, it remains unclear how these approaches identify meaningful DNA sequence signals and give insights as to why TFs bind to certain locations. In this paper, we propose a toolkit called the Deep Motif Dashboard (DeMo Dashboard) which provides a suite of visualization strategies to extract motifs, or sequence patterns from deep neural network models for TFBS classification. We demonstrate how to visualize and understand three important DNN models: convolutional, recurrent, and convolutional-recurrent networks. Our first visualization method is finding a test sequence's saliency map which uses first-order derivatives to describe the importance of each nucleotide in making the final prediction. Second, considering recurrent models make predictions in a temporal manner (from one end of a TFBS sequence to the other), we introduce temporal output scores, indicating the prediction score of a model over time for a sequential input. Lastly, a class-specific visualization strategy finds the optimal input sequence for a given TFBS positive class via stochastic gradient optimization. Our experimental results indicate that a convolutional-recurrent architecture performs the best among the three architectures. The visualization techniques indicate that CNN-RNN makes predictions by modeling both motifs as well as dependencies among them.

LGJul 7, 2016
DeepChrome: Deep-learning for predicting gene expression from histone modifications

Ritambhara Singh, Jack Lanchantin, Gabriel Robins et al.

Motivation: Histone modifications are among the most important factors that control gene regulation. Computational methods that predict gene expression from histone modification signals are highly desirable for understanding their combinatorial effects in gene regulation. This knowledge can help in developing 'epigenetic drugs' for diseases like cancer. Previous studies for quantifying the relationship between histone modifications and gene expression levels either failed to capture combinatorial effects or relied on multiple methods that separate predictions and combinatorial analysis. This paper develops a unified discriminative framework using a deep convolutional neural network to classify gene expression using histone modification data as input. Our system, called DeepChrome, allows automatic extraction of complex interactions among important features. To simultaneously visualize the combinatorial interactions among histone modifications, we propose a novel optimization-based technique that generates feature pattern maps from the learnt deep model. This provides an intuitive description of underlying epigenetic mechanisms that regulate genes. Results: We show that DeepChrome outperforms state-of-the-art models like Support Vector Machines and Random Forests for gene expression classification task on 56 different cell-types from REMC database. The output of our visualization technique not only validates the previous observations but also allows novel insights about combinatorial interactions among histone modification marks, some of which have recently been observed by experimental studies.

LGMay 10, 2016
MUST-CNN: A Multilayer Shift-and-Stitch Deep Convolutional Architecture for Sequence-based Protein Structure Prediction

Zeming Lin, Jack Lanchantin, Yanjun Qi

Predicting protein properties such as solvent accessibility and secondary structure from its primary amino acid sequence is an important task in bioinformatics. Recently, a few deep learning models have surpassed the traditional window based multilayer perceptron. Taking inspiration from the image classification domain we propose a deep convolutional neural network architecture, MUST-CNN, to predict protein properties. This architecture uses a novel multilayer shift-and-stitch (MUST) technique to generate fully dense per-position predictions on protein sequences. Our model is significantly simpler than the state-of-the-art, yet achieves better results. By combining MUST and the efficient convolution operation, we can consider far more parameters while retaining very fast prediction speeds. We beat the state-of-the-art performance on two large protein property prediction datasets.

LGMay 4, 2016
Deep Motif: Visualizing Genomic Sequence Classifications

Jack Lanchantin, Ritambhara Singh, Zeming Lin et al.

This paper applies a deep convolutional/highway MLP framework to classify genomic sequences on the transcription factor binding site task. To make the model understandable, we propose an optimization driven strategy to extract "motifs", or symbolic patterns which visualize the positive class learned by the network. We show that our system, Deep Motif (DeMo), extracts motifs that are similar to, and in some cases outperform the current well known motifs. In addition, we find that a deeper model consisting of multiple convolutional and highway layers can outperform a single convolutional and fully connected layer in the previous state-of-the-art.