Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of interest, such as catalytic activity and binding affinity to a specified target. However, the space of possible proteins is too large to search exhaustively in the laboratory, and functional proteins are scarce in the vast sequence space. Machine learning (ML) approaches can accelerate directed evolution by learning to map protein sequences to functions without building a detailed model of the underlying physics, chemistry and biological pathways. Despite the great potentials held by these ML methods, they encounter severe challenges in identifying the most suitable sequences for a targeted function. These failures can be attributed to the common practice of adopting a high-dimensional feature representation for protein sequences and inefficient search methods. To address these issues, we propose an efficient, experimental design-oriented closed-loop optimization framework for protein directed evolution, termed ODBO, which employs a combination of novel low-dimensional protein encoding strategy and Bayesian optimization enhanced with search space prescreening via outlier detection. We further design an initial sample selection strategy to minimize the number of experimental samples for training ML models. We conduct and report four protein directed evolution experiments that substantiate the capability of the proposed framework for finding of the variants with properties of interest. We expect the ODBO framework to greatly reduce the experimental cost and time cost of directed evolution, and can be further generalized as a powerful tool for adaptive experimental design in a broader context.

Failure detection in automated image classification is a critical safeguard for clinical deployment. Detected failure cases can be referred to human assessment, ensuring patient safety in computer-aided clinical decision making. Despite its paramount importance, there is insufficient evidence about the ability of state-of-the-art confidence scoring methods to detect test-time failures of classification models in the context of medical imaging. This paper provides a reality check, establishing the performance of in-domain misclassification detection methods, benchmarking 9 widely used confidence scores on 6 medical imaging datasets with different imaging modalities, in multiclass and binary classification settings. Our experiments show that the problem of failure detection is far from being solved. We found that none of the benchmarked advanced methods proposed in the computer vision and machine learning literature can consistently outperform a simple softmax baseline, demonstrating that improved out-of-distribution detection or model calibration do not necessarily translate to improved in-domain misclassification detection.

To compare performance, sample efficiency, and hidden stratification of visual transformer (ViT) and convolutional neural network (CNN) architectures for diagnosis of disease on chest radiographs and extremity radiographs using transfer learning. Performance was assessed on internal test sets and 75 000 external chest radiographs (three datasets). The primary comparison was DeiT-B ViT vs DenseNet121 CNN; secondary comparisons included DeiT-Ti (Tiny), ResNet152, and EfficientNetB7. Sample efficiency was evaluated by training models on varying dataset sizes. Hidden stratification was evaluated by comparing prevalence of chest tubes in pneumothorax false-positive and false-negative predictions and specific abnormalities for MURA false-negative predictions.

Chinmay Rane is the first author of the article " A novel attention fusion network‐based framework to ensemble the predictions of CNNs for lymph node metastasis detection." This work is from IIIT-G, India, and I personally congratulate all the authors for this piece of work. Note: Please refer to the paper for reference. Diagnosis of pathological scans of lymph node metastasis is always tricky for doctors. It is the need of the hour to help the pathologist with better disease prediction using innovative technology.

Document-level relation extraction (RE) aims to identify relations between entities across multiple sentences. Most previous methods focused on document-level RE under full supervision. However, in real-world scenario, it is expensive and difficult to completely label all relations in a document because the number of entity pairs in document-level RE grows quadratically with the number of entities. To solve the common incomplete labeling problem, we propose a unified positive-unlabeled learning framework - shift and squared ranking loss positive-unlabeled (SSR-PU) learning. We use positive-unlabeled (PU) learning on document-level RE for the first time. Considering that labeled data of a dataset may lead to prior shift of unlabeled data, we introduce a PU learning under prior shift of training data. Also, using none-class score as an adaptive threshold, we propose squared ranking loss and prove its Bayesian consistency with multi-label ranking metrics. Extensive experiments demonstrate that our method achieves an improvement of about 14 F1 points relative to the previous baseline with incomplete labeling. In addition, it outperforms previous state-of-the-art results under both fully supervised and extremely unlabeled settings as well.

Federated learning (FL) is vulnerable to model poisoning attacks, in which malicious clients corrupt the global model via sending manipulated model updates to the server. Existing defenses mainly rely on Byzantine-robust FL methods, which aim to learn an accurate global model even if some clients are malicious. However, they can only resist a small number of malicious clients in practice. It is still an open challenge how to defend against model poisoning attacks with a large number of malicious clients. Our FLDetector addresses this challenge via detecting malicious clients. FLDetector aims to detect and remove the majority of the malicious clients such that a Byzantine-robust FL method can learn an accurate global model using the remaining clients. Our key observation is that, in model poisoning attacks, the model updates from a client in multiple iterations are inconsistent. Therefore, FLDetector detects malicious clients via checking their model-updates consistency. Roughly speaking, the server predicts a client's model update in each iteration based on its historical model updates using the Cauchy mean value theorem and L-BFGS, and flags a client as malicious if the received model update from the client and the predicted model update are inconsistent in multiple iterations. Our extensive experiments on three benchmark datasets show that FLDetector can accurately detect malicious clients in multiple state-of-the-art model poisoning attacks. After removing the detected malicious clients, existing Byzantine-robust FL methods can learn accurate global models.Our code is available at https://github.com/zaixizhang/FLDetector.

Pretraining multimodal models on Electronic Health Records (EHRs) provides a means of learning representations that can transfer to downstream tasks with minimal supervision. Recent multimodal models induce soft local alignments between image regions and sentences. This is of particular interest in the medical domain, where alignments might highlight regions in an image relevant to specific phenomena described in free-text. While past work has suggested that attention "heatmaps" can be interpreted in this manner, there has been little evaluation of such alignments. We compare alignments from a state-of-the-art multimodal (image and text) model for EHR with human annotations that link image regions to sentences. Our main finding is that the text has an often weak or unintuitive influence on attention; alignments do not consistently reflect basic anatomical information. Moreover, synthetic modifications -- such as substituting "left" for "right" -- do not substantially influence highlights. Simple techniques such as allowing the model to opt out of attending to the image and few-shot finetuning show promise in terms of their ability to improve alignments with very little or no supervision. We make our code and checkpoints open-source.

Graph-based fraud detection has heretofore received considerable attention. Owning to the great success of Graph Neural Networks (GNNs), many approaches adopting GNNs for fraud detection has been gaining momentum. However, most existing methods are based on the strong inductive bias of homophily, which indicates that the context neighbors tend to have same labels or similar features. In real scenarios, fraudsters often engage in camouflage behaviors in order to avoid detection system. Therefore, the homophilic assumption no longer holds, which is known as the inconsistency problem. In this paper, we argue that the performance degradation is mainly attributed to the inconsistency between topology and attribute. To address this problem, we propose to disentangle the fraud network into two views, each corresponding to topology and attribute respectively. Then we propose a simple and effective method that uses the attention mechanism to adaptively fuse two views which captures data-specific preference. In addition, we further improve it by introducing mutual information constraints for topology and attribute. To this end, we propose a Disentangled Information Graph Neural Network (DIGNN) model, which utilizes variational bounds to find an approximate solution to our proposed optimization objective function. Extensive experiments demonstrate that our model can significantly outperform stateof-the-art baselines on real-world fraud detection datasets.

Adversarial Examples Detection (AED) is a crucial defense technique against adversarial attacks and has drawn increasing attention from the Natural Language Processing (NLP) community. Despite the surge of new AED methods, our studies show that existing methods heavily rely on a shortcut to achieve good performance. In other words, current search-based adversarial attacks in NLP stop once model predictions change, and thus most adversarial examples generated by those attacks are located near model decision boundaries. To surpass this shortcut and fairly evaluate AED methods, we propose to test AED methods with \textbf{F}ar \textbf{B}oundary (\textbf{FB}) adversarial examples. Existing methods show worse than random guess performance under this scenario. To overcome this limitation, we propose a new technique, \textbf{ADDMU}, \textbf{a}dversary \textbf{d}etection with \textbf{d}ata and \textbf{m}odel \textbf{u}ncertainty, which combines two types of uncertainty estimation for both regular and FB adversarial example detection. Our new method outperforms previous methods by 3.6 and 6.0 \emph{AUC} points under each scenario. Finally, our analysis shows that the two types of uncertainty provided by \textbf{ADDMU} can be leveraged to characterize adversarial examples and identify the ones that contribute most to model's robustness in adversarial training.

While recent work has convincingly showed that sequence-to-sequence models struggle to generalize to new compositions (termed compositional generalization), little is known on what makes compositional generalization hard on a particular test instance. In this work, we investigate what are the factors that make generalization to certain test instances challenging. We first substantiate that indeed some examples are more difficult than others by showing that different models consistently fail or succeed on the same test instances. Then, we propose a criterion for the difficulty of an example: a test instance is hard if it contains a local structure that was not observed at training time. We formulate a simple decision rule based on this criterion and empirically show it predicts instance-level generalization well across 5 different semantic parsing datasets, substantially better than alternative decision rules. Last, we show local structures can be leveraged for creating difficult adversarial compositional splits and also to improve compositional generalization under limited training budgets by strategically selecting examples for the training set.