Antibodies have become an important class of therapeutic agents to treat human diseases.To accelerate therapeutic antibody discovery, computational methods, especially machine learning, have attracted considerable interest for predicting specific interactions between antibody candidates and target antigens such as viruses and bacteria.However, the publicly available datasets in existing works have notable limitations, such as small sizes and the lack of non-binding samples and exact amino acid sequences.To overcome these limitations, we have developed AVIDa-hIL6, a large-scale dataset for predicting antigen-antibody interactions in the variable domain of heavy chain of heavy chain antibodies (VHHs), produced from an alpaca immunized with the human interleukin-6 (IL-6) protein, as antigens.By leveraging the simple structure of VHHs, which facilitates identification of full-length amino acid sequences by DNA sequencing technology, AVIDa-hIL6 contains 573,891 antigen-VHH pairs with amino acid sequences.All the antigen-VHH pairs have reliable labels for binding or non-binding, as generated by a novel labeling method.Furthermore, via introduction of artificial mutations, AVIDa-hIL6 contains 30 different mutants in addition to wild-type IL-6 protein.This characteristic provides opportunities to develop machine learning models for predicting changes in antibody binding by antigen mutations.We report experimental benchmark results on AVIDa-hIL6 by using machine learning models.The results indicate that the existing models have potential, but further research is needed to generalize them to predict effective antibodies against unknown mutants.The dataset is available at https://avida-hil6.cognanous.com.

Many contemporary machine learning models require extensive tuning of hyperparameters to perform well. A variety of methods, such as Bayesian optimization, have been developed to automate and expedite this process. However, tuning remains extremely costly as it typically requires repeatedly fully training models. To address this issue, Bayesian optimization methods have been extended to use cheap, partially trained models to extrapolate to expensive complete models. While this approach enlarges the set of explored hyperparameters, including many low-fidelity observations adds to the intrinsic randomness of the procedure and makes extrapolation challenging. We propose to accelerate hyperparameter tuning for neural networks in a robust way by taking into account the relative amount of information contributed by each training example. To do so, we integrate importance sampling with Bayesian optimization, which significantly increases the quality of the black-box function evaluations and their runtime. To overcome the additional overhead cost of using importance sampling, we cast hyperparameter search as a multi-task Bayesian optimization problem over both hyperparameters and importance sampling design, which achieves the best of both worlds. Through learning a trade-off between training complexity and quality, our method improves upon validation error, in the average and worst-case. We show that this results in more reliable performance of our method in less wall-clock time across a variety of and datasets complex neural architectures.

The use of black-box optimization for the design of new biological sequences is an emerging research area with potentially revolutionary impact. The cost and latency of wet-lab experiments requires methods that find good sequences in few experimental rounds of large batches of sequences — a setting that off-the-shelf black-box optimization methods are ill-equipped to handle. We find that the performance of existing methods varies drastically across optimization tasks, posing a significant obstacle to real-world applications. To improve robustness, we propose Population-Based Black-Box Optimization (P3BO), which generates batches of sequences by sampling from an ensemble of methods. The number of sequences sampled from any method is proportional to the quality of sequences it previously proposed, allowing P3BO to combine the strengths of individual methods while hedging against their innate brittleness. Adapting the hyper-parameters of each of the methods online using evolutionary optimization further improves performance. Through extensive experiments on in-silico optimization tasks, we show that P3BO outperforms any single method in its population, proposing higher quality sequences as well as more diverse batches. As such, P3BO and Adaptive-P3BO are a crucial step towards deploying ML to real-world sequence design.

Determinantal Point Processes (DPPs) have attracted significant interest from the machine-learning community due to their ability to elegantly and tractably model the delicate balance between quality and diversity of sets. DPPs are commonly learned from data using maximum likelihood estimation (MLE). While fitting observed sets well, MLE for DPPs may also assign high likelihoods to unobserved sets that are far from the true generative distribution of the data. To address this issue, which reduces the quality of the learned model, we introduce a novel optimization problem, Contrastive Estimation (CE), which encodes information about "negative" samples into the basic learning model. CE is grounded in the successful use of negative information in machine-vision and language modeling. Depending on the chosen negative distribution (which may be static or evolve during optimization), CE assumes two different forms, which we analyze theoretically and experimentally. We evaluate our new model on real-world datasets; on a challenging dataset, CE learning delivers a considerable improvement in predictive performance over a DPP learned without using contrastive information.

The availability of large amounts of time series data, paired with the performance of deep-learning algorithms on a broad class of problems, has recently led to significant interest in the use of sequence-to-sequence models for time series forecasting. We provide the first theoretical analysis of this time series forecasting framework. We include a comparison of sequence-to-sequence modeling to classical time series models, and as such our theory can serve as a quantitative guide for practitioners choosing between different modeling methodologies.

It is often desirable in recommender systems and other information retrieval applications to provide diverse results, and determinantal point processes (DPPs) have become a popular way to capture the trade-off between the quality of individual results and the diversity of the overall set. However, sampling from a DPP is inherently expensive: if the underlying collection contains N items, then generating each DPP sample requires time linear in N following a one-time preprocessing phase. Additionally, results often need to be personalized to a user, but standard approaches to personalization invalidate the preprocessing, making personalized samples especially expensive. In this work we address both of these shortcomings. First, we propose a new algorithm for generating DPP samples in time logarithmic in N, following a slightly more expensive preprocessing phase. We then extend the algorithm to support arbitrary query-time feature weights, allowing us to generate samples customized to individual users while still retaining logarithmic runtime; experiments show our approach runs over 300 times faster than traditional DPP sampling on collections of 100,000 items for samples of size 10.

Determinantal point processes (DPPs) provide an elegant and versatile way to sample sets of items that balance the point-wise quality with the set-wise diversity of selected items. For this reason, they have gained prominence in many machine learning applications that rely on subset selection. However, sampling from a DPP over a ground set of size N is a costly operation, requiring in general an O(N^3) preprocessing cost and an O(Nk^3) sampling cost for subsets of size k. We approach this problem by introducing DppNets: generative deep models that produce DPP-like samples for arbitrary ground sets. We develop an inhibitive attention mechanism based on transformer networks that captures a notion of dissimilarity between feature vectors. We show theoretically that such an approximation is sensible as it maintains the guarantees of inhibition or dissimilarity that makes DPPs so powerful and unique. Empirically, we show across multiple datasets that DPPNET is orders of magnitude faster than competing approaches for DPP sampling, while generating high-likelihood samples and performing as well as DPPs on downstream tasks.

Determinantal point processes (DPPs) are well-suited to recommender systems where the goal is to generate collections of diverse, high-quality items. In the existing literature this is usually formulated as finding the mode of the DPP (the so-called MAP set). However, the MAP objective inherently assumes that the DPP models "optimal" recommendation sets, and yet obtaining such a DPP is nontrivial when there is no ready source of example optimal sets. In this paper we advocate an alternative framework for applying DPPs to recommender systems. Our approach assumes that the DPP simply models user engagements with recommended items, which is more consistent with how DPPs for recommender systems are typically trained. With this assumption, we are able to formulate a metric that measures the expected number of items that a user will engage with. We formalize this optimization of this metric as the Maximum Induced Cardinality (MIC) problem. Although the MIC objective is not submodular, we show that it can be approximated by a submodular function, and that empirically it is well-optimized by a greedy algorithm.

Strongly Rayleigh (SR) measures are discrete probability distributions over the subsets of a ground set. They enjoy strong negative dependence properties, as a result of which they assign higher probability to subsets of diverse elements. We introduce in this paper Exponentiated Strongly Rayleigh (ESR) measures, which sharpen (or smoothen) the negative dependence property of SR measures via a single parameter (the exponent) that can intuitively understood as an inverse temperature. We develop efficient MCMC procedures for approximate sampling from ESRs, and obtain explicit mixing time bounds for two concrete instances: exponentiated versions of Determinantal Point Processes and Dual Volume Sampling. We illustrate some of the potential of ESRs, by applying them to a few machine learning tasks; empirical results confirm that beyond their theoretical appeal, ESR-based models hold significant promise for these tasks.

We revisit the classical problem of optimal experimental design (OED) under a new mathematical model grounded in a geometric motivation. Specifically, we introduce models based on elementary symmetric polynomials; these polynomials capture "partial volumes" and offer a graded interpolation between the widely used A-optimal and D-optimal design models, obtaining each of them as special cases. We analyze properties of our models, and derive both greedy and convex-relaxation algorithms for computing the associated designs. Our analysis establishes approximation guarantees on these algorithms, while our empirical results substantiate our claims and demonstrate a curious phenomenon concerning our greedy algorithm. Finally, as a byproduct, we obtain new results on the theory of elementary symmetric polynomials that may be of independent interest.

Determinantal Point Processes (DPPs) are probabilistic models over all subsets a ground set of N items. They have recently gained prominence in several applications that rely on diverse subsets. However, their applicability to large problems is still limited due to O(N^3) complexity of core tasks such as sampling and learning. We enable efficient sampling and learning for DPPs by introducing KronDPP, a DPP model whose kernel matrix decomposes as a tensor product of multiple smaller kernel matrices. This decomposition immediately enables fast exact sampling. But contrary to what one may expect, leveraging the Kronecker product structure for speeding up DPP learning turns out to be more difficult. We overcome this challenge, and derive batch and stochastic optimization algorithms for efficiently learning the parameters of a KronDPP.

Determinantal point processes (DPPs) offer an elegant tool for encoding probabilities over subsets of a ground set. Discrete DPPs are parametrized by a positive semidefinite matrix (called the DPP kernel), and estimating this kernel is key to learning DPPs from observed data. We consider the task of learning the DPP kernel, and develop for it a surprisingly simple yet effective new algorithm. Our algorithm offers the following benefits over previous approaches: (a) it is much simpler; (b) it yields equally good and sometimes even better local maxima; and (c) it runs an order of magnitude faster on large problems. We present experimental results on both real and simulated data to illustrate the numerical performance of our technique.