Cancer remains a global challenge due to its growing clinical and economic burden. Its uniquely personal manifestation, which makes treatment difficult, has fuelled the quest for personalized treatment strategies. Thus, genomic profiling is increasingly becoming part of clinical diagnostic panels. Effective use of such panels requires accurate drug response prediction (DRP) models, which are challenging to build due to limited labelled patient data. Previous methods to address this problem have used various forms of transfer learning. However, they do not explicitly model the variable length sequential structure of the list of mutations in such diagnostic panels. Further, they do not utilize auxiliary information (like patient survival) for model training. We address these limitations through a novel transformer based method, which surpasses the performance of state-of-the-art DRP models on benchmark data. We also present the design of a treatment recommendation system (TRS), which is currently deployed at the National University Hospital, Singapore and is being evaluated in a clinical trial.

The Gradient Descent-Ascent (GDA) algorithm, designed to solve minimax optimization problems, takes the descent and ascent steps either simultaneously (Sim-GDA) or alternately (Alt-GDA). While Alt-GDA is commonly observed to converge faster, the performance gap between the two is not yet well understood theoretically, especially in terms of global convergence rates. To address this theory-practice gap, we present fine-grained convergence analyses of both algorithms for strongly-convex-strongly-concave and Lipschitz-gradient objectives. Our new iteration complexity upper bound of Alt-GDA is strictly smaller than the lower bound of Sim-GDA; i.e., Alt-GDA is provably faster. Moreover, we propose Alternating-Extrapolation GDA (Alex-GDA), a general algorithmic framework that subsumes Sim-GDA and Alt-GDA, for which the main idea is to alternately take gradients from extrapolations of the iterates. We show that Alex-GDA satisfies a smaller iteration complexity bound, identical to that of the Extra-gradient method, while requiring less gradient computations. We also prove that Alex-GDA enjoys linear convergence for bilinear problems, for which both Sim-GDA and Alt-GDA fail to converge at all.

We study the use of linear regression for multiclass classification in the over-parametrized regime where some of the training data is mislabeled. In such scenarios it is necessary to add an explicit regularization term, $\lambda f(w)$, for some convex function $f(\cdot)$, to avoid overfitting the mislabeled data. In our analysis, we assume that the data is sampled from a Gaussian Mixture Model with equal class sizes, and that a proportion $c$ of the training labels is corrupted for each class. Under these assumptions, we prove that the best classification performance is achieved when $f(\cdot) = \|\cdot\|^2_2$ and $\lambda \to \infty$. We then proceed to analyze the classification errors for $f(\cdot) = \|\cdot\|_1$ and $f(\cdot) = \|\cdot\|_\infty$ in the large $\lambda$ regime and notice that it is often possible to find sparse and one-bit solutions, respectively, that perform almost as well as the one corresponding to $f(\cdot) = \|\cdot\|_2^2$.

Graph contrastive learning (GCL) has emerged as a pivotal technique in the domain of graph representation learning. A crucial aspect of effective GCL is the caliber of generated positive and negative samples, which is intrinsically dictated by their resemblance to the original data. Nevertheless, precise control over similarity during sample generation presents a formidable challenge, often impeding the effective discovery of representative graph patterns. To address this challenge, we propose an innovative framework: Adversarial Curriculum Graph Contrastive Learning (ACGCL), which capitalizes on the merits of pair-wise augmentation to engender graph-level positive and negative samples with controllable similarity, alongside subgraph contrastive learning to discern effective graph patterns therein. Within the ACGCL framework, we have devised a novel adversarial curriculum training methodology that facilitates progressive learning by sequentially increasing the difficulty of distinguishing the generated samples. Notably, this approach transcends the prevalent sparsity issue inherent in conventional curriculum learning strategies by adaptively concentrating on more challenging training data. Finally, a comprehensive assessment of ACGCL is conducted through extensive experiments on six well-known benchmark datasets, wherein ACGCL conspicuously surpasses a set of state-of-the-art baselines.

Transformers have improved drastically the performance of natural language processing (NLP) and computer vision applications. The computation of transformers involves matrix multiplications and non-linear activation functions such as softmax and GELU (Gaussion Error Linear Unit) that are accelerated directly in hardware. Currently, function evaluation is done separately for each function and rarely allows for hardware reuse. To mitigate this problem, in this work, we map the computation of GELU to a softmax operator. In this way, the efficient hardware units designed already for softmax can be reused for computing GELU as well. Computation of GELU can enjoy the inherent vectorized nature of softmax and produce in parallel multiple GELU outcomes. Experimental results show that computing GELU via a pre-existing and incrementally modified softmax hardware unit (a) does not reduce the accuracy of representative NLP applications and (b) allows the reduction of the overall hardware area and power by 6.1% and 11.9%, respectively, on average.

Language models often exhibit undesirable behaviors, such as gender bias or toxic language. Interventions in the representation space were shown effective in mitigating such issues by altering the LM behavior. We first show that two prominent intervention techniques, Linear Erasure and Steering Vectors, do not enable a high degree of control and are limited in expressivity. We then propose a novel intervention methodology for generating expressive counterfactuals in the representation space, aiming to make representations of a source class (e.g., "toxic") resemble those of a target class (e.g., "non-toxic"). This approach, generalizing previous linear intervention techniques, utilizes a closed-form solution for the Earth Mover's problem under Gaussian assumptions and provides theoretical guarantees on the representation space's geometric organization. We further build on this technique and derive a nonlinear intervention that enables controlled generation. We demonstrate the effectiveness of the proposed approaches in mitigating bias in multiclass classification and in reducing the generation of toxic language, outperforming strong baselines.

It is desirable in many multi-objective machine learning applications, such as multi-task learning with conflicting objectives and multi-objective reinforcement learning, to find a Pareto solution that can match a given preference of a decision maker. These problems are often large-scale with available gradient information but cannot be handled very well by the existing algorithms. To tackle this critical issue, this paper proposes a novel predict-and-correct framework for locating a Pareto solution that fits the preference of a decision maker. In the proposed framework, a constraint function is introduced in the search progress to align the solution with a user-specific preference, which can be optimized simultaneously with multiple objective functions. Experimental results show that our proposed method can efficiently find a particular Pareto solution under the demand of a decision maker for standard multiobjective benchmark, multi-task learning, and multi-objective reinforcement learning problems with more than thousands of decision variables. Code is available at: https://github.com/xzhang2523/pmgda. Our code is current provided in the pgmda.rar attached file and will be open-sourced after publication.}

Selecting high-quality pre-training data is important for creating capable language models, but existing methods rely on simple heuristics. We introduce QuRating, a method for selecting pre-training data that captures the abstract qualities of texts which humans intuitively perceive. In this paper, we investigate four qualities - writing style, required expertise, facts & trivia, and educational value. We find that LLMs are able to discern these qualities and observe that they are better at making pairwise judgments of texts than at rating the quality of a text directly. We train a QuRater model to learn scalar ratings from pairwise judgments, and use it to annotate a 260B training corpus with quality ratings for each of the four criteria. In our experiments, we select 30B tokens according to the different quality ratings and train 1.3B-parameter language models on the selected data. We find that it is important to balance quality and diversity, as selecting only the highest-rated documents leads to poor results. When we sample using quality ratings as logits over documents, our models achieve lower perplexity and stronger in-context learning performance than baselines. Beyond data selection, we use the quality ratings to construct a training curriculum which improves performance without changing the training dataset. We extensively analyze the quality ratings and discuss their characteristics, biases, and wider implications.

Global ambient air pollution, a transboundary challenge, is typically addressed through interventions relying on data from spatially sparse and heterogeneously placed monitoring stations. These stations often encounter temporal data gaps due to issues such as power outages. In response, we have developed a scalable, data-driven, supervised machine learning framework. This model is designed to impute missing temporal and spatial measurements, thereby generating a comprehensive dataset for pollutants including NO$_2$, O$_3$, PM$_{10}$, PM$_{2.5}$, and SO$_2$. The dataset, with a fine granularity of 0.25$^{\circ}$ at hourly intervals and accompanied by prediction intervals for each estimate, caters to a wide range of stakeholders relying on outdoor air pollution data for downstream assessments. This enables more detailed studies. Additionally, the model's performance across various geographical locations is examined, providing insights and recommendations for strategic placement of future monitoring stations to further enhance the model's accuracy.

The report describes the discussions from the Workshop on Mathematical Opportunities in Digital Twins (MATH-DT) from December 11-13, 2023, George Mason University. It illustrates that foundational Mathematical advances are required for Digital Twins (DTs) that are different from traditional approaches. A traditional model, in biology, physics, engineering or medicine, starts with a generic physical law (e.g., equations) and is often a simplification of reality. A DT starts with a specific ecosystem, object or person (e.g., personalized care) representing reality, requiring multi -scale, -physics modeling and coupling. Thus, these processes begin at opposite ends of the simulation and modeling pipeline, requiring different reliability criteria and uncertainty assessments. Additionally, unlike existing approaches, a DT assists humans to make decisions for the physical system, which (via sensors) in turn feeds data into the DT, and operates for the life of the physical system. While some of the foundational mathematical research can be done without a specific application context, one must also keep specific applications in mind for DTs. E.g., modeling a bridge or a biological system (a patient), or a socio-technical system (a city) is very different. The models range from differential equations (deterministic/uncertain) in engineering, to stochastic in biology, including agent-based. These are multi-scale hybrid models or large scale (multi-objective) optimization problems under uncertainty. There are no universal models or approaches. For e.g., Kalman filters for forecasting might work in engineering, but can fail in biomedical domain. Ad hoc studies, with limited systematic work, have shown that AI/ML methods can fail for simple engineering systems and can work well for biomedical problems. A list of `Mathematical Opportunities and Challenges' concludes the report.