arXiv subjects

Justin Hong

Publications and source records attributed to Justin Hong.

6 recordsLinked to original sources

arXiv2026

Optimizing RNA yield using deep neural networks coupled to massively parallel screening

Messenger RNA (mRNA)-based therapeutics have emerged as a powerful platform for vaccines, protein replacement therapies, and cancer immunotherapy. A critical bottleneck in mRNA development is manufacturing large quantities of RNA economically, as measured by RNA yield emerging from an in vitro transcription (IVT) reaction. However, how promoter-adjacent DNA sequences influence RNA yield remains poorly characterized. Here, we present an integrated deep learning framework that leverages massively parallel next-generation sequencing (NGS) assays to measure RNA yield across large sequence spaces. A library of 10^5 randomized oligonucleotide sequences was designed to systematically explore sequence diversity within a defined structural context. DNA and RNA abundances were quantified in parallel using Illumina sequencing, enabling high-resolution measurement of sequence-to-yield relationships at scale. Sequences were one-hot encoded and used to train deep learning models, using a convolutional neural network architecture. The model achieved a Pearson correlation of 0.94 between predicted and experimentally measured RNA yield on a held-out test set, demonstrating strong generalization across diverse sequence contexts. Importantly, the trained model can be deployed in a production environment to score and rank novel RNA sequence designs by predicted IVT yield, enabling cost-effective, pre-experimental prioritization of the most manufacturable candidates. This framework establishes a scalable, data-driven approach to DNA and RNA sequence optimization, with broad applicability to vaccine antigen design, therapeutic protein delivery, and synthetic biology. By integrating high-throughput experimentation with advanced deep learning modeling, it significantly reduces screening costs and accelerates RNA engineering cycle times.

q-bio.GN↗

arXiv2023

Stable Differentiable Causal Discovery

Inferring causal relationships as directed acyclic graphs (DAGs) is an important but challenging problem. Differentiable Causal Discovery (DCD) is a promising approach to this problem, framing the search as a continuous optimization. But existing DCD methods are numerically unstable, with poor performance beyond tens of variables. In this paper, we propose Stable Differentiable Causal Discovery (SDCD), a new method that improves previous DCD methods in two ways: (1) It employs an alternative constraint for acyclicity; this constraint is more stable, both theoretically and empirically, and fast to compute. (2) It uses a training procedure tailored for sparse causal graphs, which are common in real-world scenarios. We first derive SDCD and prove its stability and correctness. We then evaluate it with both observational and interventional data and on both small-scale and large-scale settings. We find that SDCD outperforms existing methods in both convergence speed and accuracy and can scale to thousands of variables. We provide code at https://github.com/azizilab/sdcd.

cs.LG↗

arXiv2023

The CausalBench challenge: A machine learning contest for gene network inference from single-cell perturbation data

In drug discovery, mapping interactions between genes within cellular systems is a crucial early step. Such maps are not only foundational for understanding the molecular mechanisms underlying disease biology but also pivotal for formulating hypotheses about potential targets for new medicines. Recognizing the need to elevate the construction of these gene-gene interaction networks, especially from large-scale, real-world datasets of perturbed single cells, the CausalBench Challenge was initiated. This challenge aimed to inspire the machine learning community to enhance state-of-the-art methods, emphasizing better utilization of expansive genetic perturbation data. Using the framework provided by the CausalBench benchmark, participants were tasked with refining the current methodologies or proposing new ones. This report provides an analysis and summary of the methods submitted during the challenge to give a partial image of the state of the art at the time of the challenge. Notably, the winning solutions significantly improved performance compared to previous baselines, establishing a new state of the art for this critical task in biology and medicine.

cs.LG↗

arXiv2020

The Field Substellar Mass Function Based on the Full-sky 20-pc Census of 525 L, T, and Y Dwarfs

We present final Spitzer trigonometric parallaxes for 361 L, T, and Y dwarfs. We combine these with prior studies to build a list of 525 known L, T, and Y dwarfs within 20 pc of the Sun, 38 of which are presented here for the first time. Using published photometry and spectroscopy as well as our own follow-up, we present an array of color-magnitude and color-color diagrams to further characterize census members, and we provide polynomial fits to the bulk trends. Using these characterizations, we assign each object a $T_{\rm eff}$ value and judge sample completeness over bins of $T_{\rm eff}$ and spectral type. Except for types $\ge$ T8 and $T_{\rm eff} <$ 600K, our census is statistically complete to the 20-pc limit. We compare our measured space densities to simulated density distributions and find that the best fit is a power law ($dN/dM \propto M^{-\alpha}$) with $\alpha = 0.6{\pm}0.1$. We find that the evolutionary models of Saumon & Marley correctly predict the observed magnitude of the space density spike seen at 1200K $< T_{\rm eff} <$ 1350K, believed to be caused by an increase in the cooling timescale across the L/T transition. Defining the low-mass terminus using this sample requires a more statistically robust and complete sample of dwarfs $\ge$Y0.5 and with $T_{\rm eff} <$ 400K. We conclude that such frigid objects must exist in substantial numbers, despite the fact that few have so far been identified, and we discuss possible reasons why they have largely eluded detection.

astro-ph.SR↗

arXiv2020

Towards ML Engineering: A Brief History Of TensorFlow Extended (TFX)

Software Engineering, as a discipline, has matured over the past 5+ decades. The modern world heavily depends on it, so the increased maturity of Software Engineering was an eventuality. Practices like testing and reliable technologies help make Software Engineering reliable enough to build industries upon. Meanwhile, Machine Learning (ML) has also grown over the past 2+ decades. ML is used more and more for research, experimentation and production workloads. ML now commonly powers widely-used products integral to our lives. But ML Engineering, as a discipline, has not widely matured as much as its Software Engineering ancestor. Can we take what we have learned and help the nascent field of applied ML evolve into ML Engineering the way Programming evolved into Software Engineering [1]? In this article we will give a whirlwind tour of Sibyl [2] and TensorFlow Extended (TFX) [3], two successive end-to-end (E2E) ML platforms at Alphabet. We will share the lessons learned from over a decade of applied ML built on these platforms, explain both their similarities and their differences, and expand on the shifts (both mental and technical) that helped us on our journey. In addition, we will highlight some of the capabilities of TFX that help realize several aspects of ML Engineering. We argue that in order to unlock the gains ML can bring, organizations should advance the maturity of their ML teams by investing in robust ML infrastructure and promoting ML Engineering education. We also recommend that before focusing on cutting-edge ML modeling techniques, product leaders should invest more time in adopting interoperable ML platforms for their organizations. In closing, we will also share a glimpse into the future of TFX.

cs.SE↗

arXiv2019

Robust Federated Learning in a Heterogeneous Environment

We study a recently proposed large-scale distributed learning paradigm, namely Federated Learning, where the worker machines are end users' own devices. Statistical and computational challenges arise in Federated Learning particularly in the presence of heterogeneous data distribution (i.e., data points on different devices belong to different distributions signifying different clusters) and Byzantine machines (i.e., machines that may behave abnormally, or even exhibit arbitrary and potentially adversarial behavior). To address the aforementioned challenges, first we propose a general statistical model for this problem which takes both the cluster structure of the users and the Byzantine machines into account. Then, leveraging the statistical model, we solve the robust heterogeneous Federated Learning problem \emph{optimally}; in particular our algorithm matches the lower bound on the estimation error in dimension and the number of data points. Furthermore, as a by-product, we prove statistical guarantees for an outlier-robust clustering algorithm, which can be considered as the Lloyd algorithm with robust estimation. Finally, we show via synthetic as well as real data experiments that the estimation error obtained by our proposed algorithm is significantly better than the non-Byzantine-robust algorithms; in particular, we gain at least by 53\% and 33\% for synthetic and real data experiments, respectively, in typical settings.

cs.LG↗