Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (<50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.

Vision transformers (ViTs) encoding an image as a sequence of patches bring new paradigms for semantic segmentation.We present an efficient framework of representation separation in local-patch level and global-region level for semantic segmentation with ViTs. It is targeted for the peculiar over-smoothness of ViTs in semantic segmentation, and therefore differs from current popular paradigms of context modeling and most existing related methods reinforcing the advantage of attention. We first deliver the decoupled two-pathway network in which another pathway enhances and passes down local-patch discrepancy complementary to global representations of transformers. We then propose the spatially adaptive separation module to obtain more separate deep representations and the discriminative cross-attention which yields more discriminative region representations through novel auxiliary supervisions. The proposed methods achieve some impressive results: 1) incorporated with large-scale plain ViTs, our methods achieve new state-of-the-art performances on five widely used benchmarks; 2) using masked pre-trained plain ViTs, we achieve 68.9% mIoU on Pascal Context, setting a new record; 3) pyramid ViTs integrated with the decoupled two-pathway network even surpass the well-designed high-resolution ViTs on Cityscapes; 4) the improved representations by our framework have favorable transferability in images with natural corruptions. The codes will be released publicly.

Question: Can an encoder-decoder architecture pretrained on a large dataset of longitudinal electronic health records improves patient outcome predictions? Findings: In this prognostic study of 6.8 million patients, our denoising sequence-to-sequence prediction model of multiple outcomes outperformed state-of-the-art models scuh pretrained BERT on a broad range of patient outcomes, including intentional self-harm and pancreatic cancer. Meaning: Deep bidirectional and autoregressive representation improves patient outcome prediction.

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Importance: Social determinants of health (SDOH) are known to be associated with increased risk of suicidal behaviors, but few studies utilized SDOH from unstructured electronic health record (EHR) notes. Objective: To investigate associations between suicide and recent SDOH, identified using structured and unstructured data. Design: Nested case-control study. Setting: EHR data from the US Veterans Health Administration (VHA). Participants: 6,122,785 Veterans who received care in the US VHA between October 1, 2010, and September 30, 2015. Exposures: Occurrence of SDOH over a maximum span of two years compared with no occurrence of SDOH. Main Outcomes and Measures: Cases of suicide deaths were matched with 4 controls on birth year, cohort entry date, sex, and duration of follow-up. We developed an NLP system to extract SDOH from unstructured notes. Structured data, NLP on unstructured data, and combining them yielded seven, eight and nine SDOH respectively. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results: In our cohort, 8,821 Veterans committed suicide during 23,725,382 person-years of follow-up (incidence rate 37.18 /100,000 person-years). Our cohort was mostly male (92.23%) and white (76.99%). Across the six common SDOH as covariates, NLP-extracted SDOH, on average, covered 84.38% of all SDOH occurrences. All SDOH, measured by structured data and NLP, were significantly associated with increased risk of suicide. The SDOH with the largest effects was legal problems (aOR=2.67, 95% CI=2.46-2.89), followed by violence (aOR=2.26, 95% CI=2.11-2.43). NLP-extracted and structured SDOH were also associated with suicide. Conclusions and Relevance: NLP-extracted SDOH were always significantly associated with increased risk of suicide among Veterans, suggesting the potential of NLP in public health studies.

As the societal impact of Deep Neural Networks (DNNs) grows, the goals for advancing DNNs become more complex and diverse, ranging from improving a conventional model accuracy metric to infusing advanced human virtues such as fairness, accountability, transparency (FaccT), and unbiasedness. Recently, techniques in Explainable Artificial Intelligence (XAI) are attracting considerable attention, and have tremendously helped Machine Learning (ML) engineers in understanding AI models. However, at the same time, we started to witness the emerging need beyond XAI among AI communities; based on the insights learned from XAI, how can we better empower ML engineers in steering their DNNs so that the model's reasonableness and performance can be improved as intended? This article provides a timely and extensive literature overview of the field Explanation-Guided Learning (EGL), a domain of techniques that steer the DNNs' reasoning process by adding regularization, supervision, or intervention on model explanations. In doing so, we first provide a formal definition of EGL and its general learning paradigm. Secondly, an overview of the key factors for EGL evaluation, as well as summarization and categorization of existing evaluation procedures and metrics for EGL are provided. Finally, the current and potential future application areas and directions of EGL are discussed, and an extensive experimental study is presented aiming at providing comprehensive comparative studies among existing EGL models in various popular application domains, such as Computer Vision (CV) and Natural Language Processing (NLP) domains.

Objective: Evictions are involved in a cascade of negative events that can lead to unemployment, homelessness, long-term poverty, and mental health problems. In this study, we developed a natural language processing system to automatically detect eviction incidences and their attributes from electronic health record (EHR) notes. Materials and Methods: We annotated eviction status in 5000 EHR notes from the Veterans Health Administration. We developed a novel model, called Knowledge Injection based on Ripple Effects of Social and Behavioral Determinants of Health (KIRESH), that has shown to substantially outperform other state-of-the-art models such as fine-tuning pre-trained language models like BioBERT and Bio_ClinicalBERT. Moreover, we designed a prompt to further improve the model performance by using the intrinsic connection between the two sub-tasks of eviction presence and period prediction. Finally, we used the Temperature Scaling-based Calibration on our KIRESH-Prompt method to avoid over-confidence issues arising from the imbalance dataset. Results: KIRESH-Prompt achieved a Macro-F1 of 0.6273 (presence) and 0.7115 (period), which was significantly higher than 0.5382 (presence) and 0.67167 (period) for just fine-tuning Bio_ClinicalBERT model. Conclusion and Future Work: KIRESH-Prompt has substantially improved eviction status classification. In future work, we will evaluate the generalizability of the model framework to other applications.

The matrix-based R\'enyi's entropy allows us to directly quantify information measures from given data, without explicit estimation of the underlying probability distribution. This intriguing property makes it widely applied in statistical inference and machine learning tasks. However, this information theoretical quantity is not robust against noise in the data, and is computationally prohibitive in large-scale applications. To address these issues, we propose a novel measure of information, termed low-rank matrix-based R\'enyi's entropy, based on low-rank representations of infinitely divisible kernel matrices. The proposed entropy functional inherits the specialty of of the original definition to directly quantify information from data, but enjoys additional advantages including robustness and effective calculation. Specifically, our low-rank variant is more sensitive to informative perturbations induced by changes in underlying distributions, while being insensitive to uninformative ones caused by noises. Moreover, low-rank R\'enyi's entropy can be efficiently approximated by random projection and Lanczos iteration techniques, reducing the overall complexity from $\mathcal{O}(n^3)$ to $\mathcal{O}(n^2 s)$ or even $\mathcal{O}(ns^2)$, where $n$ is the number of data samples and $s \ll n$. We conduct large-scale experiments to evaluate the effectiveness of this new information measure, demonstrating superior results compared to matrix-based R\'enyi's entropy in terms of both performance and computational efficiency.

Machine Learning (ML) interatomic models and potentials have been widely employed in simulations of materials. Long-range interactions often dominate in some ionic systems whose dynamics behavior is significantly influenced. However, the long-range effect such as Coulomb and Van der Wales potential is not considered in most ML interatomic potentials. To address this issue, we put forward a method that can take long-range effects into account for most ML local interatomic models with the reciprocal space neural network. The structure information in real space is firstly transformed into reciprocal space and then encoded into a reciprocal space potential or a global descriptor with full atomic interactions. The reciprocal space potential and descriptor keep full invariance of Euclidean symmetry and choice of the cell. Benefiting from the reciprocal-space information, ML interatomic models can be extended to describe the long-range potential including not only Coulomb but any other long-range interaction. A model NaCl system considering Coulomb interaction and the GaxNy system with defects are applied to illustrate the advantage of our approach. At the same time, our approach helps to improve the prediction accuracy of some global properties such as the band gap where the full atomic interaction beyond local atomic environments plays a very important role. In summary, our work has expanded the ability of current ML interatomic models and potentials when dealing with the long-range effect, hence paving a new way for accurate prediction of global properties and large-scale dynamic simulations of systems with defects.

Automatic International Classification of Diseases (ICD) coding aims to assign multiple ICD codes to a medical note with an average of 3,000+ tokens. This task is challenging due to the high-dimensional space of multi-label assignment (155,000+ ICD code candidates) and the long-tail challenge - Many ICD codes are infrequently assigned yet infrequent ICD codes are important clinically. This study addresses the long-tail challenge by transforming this multi-label classification task into an autoregressive generation task. Specifically, we first introduce a novel pretraining objective to generate free text diagnoses and procedure using the SOAP structure, the medical logic physicians use for note documentation. Second, instead of directly predicting the high dimensional space of ICD codes, our model generates the lower dimension of text descriptions, which then infer ICD codes. Third, we designed a novel prompt template for multi-label classification. We evaluate our Generation with Prompt model with the benchmark of all code assignment (MIMIC-III-full) and few shot ICD code assignment evaluation benchmark (MIMIC-III-few). Experiments on MIMIC-III-few show that our model performs with a marco F1 30.2, which substantially outperforms the previous MIMIC-III-full SOTA model (marco F1 4.3) and the model specifically designed for few/zero shot setting (marco F1 18.7). Finally, we design a novel ensemble learner, a cross attention reranker with prompts, to integrate previous SOTA and our best few-shot coding predictions. Experiments on MIMIC-III-full show that our ensemble learner substantially improves both macro and micro F1, from 10.4 to 14.6 and from 58.2 to 59.1, respectively.