Training of Template-Specific Weighted Energy Function for Sequence-to-Structure Alignment

Threading is a protein structure prediction method that uses a library of template protein structures in the following steps: first the target sequence is matched to the template library and the best template structure is selected, secondly the predicted target structure of the target sequence is modeled by this selected template structure. The deceleration of new folds which are added to the protein data bank promises completion of the template structure library. This thesis uses a new set of template-specific weights to improve the energy function for sequence-to-structure alignment in the template selection step of the threading process. The weights are estimated using least squares methods with the quality of the modelling step in the threading process as the label. These new weights show an average 12.74% improvement in estimating the label. Further family analysis show a correlation between the performance of the new weights to the number of seeds in pFam

Discovery and Analysis of Aligned Pattern Clusters from Protein Family Sequences

Protein sequences are essential for encoding molecular structures and functions. Consequently, biologists invest substantial resources and time discovering functional patterns in proteins. Using high-throughput technologies, biologists are generating an increasing amount of data. Thus, the major challenge in biosequencing today is the ability to conduct data analysis in an effi cient and productive manner. Conserved amino acids in proteins reveal important functional domains within protein families. Conversely, less conserved amino acid variations within these protein sequence patterns reveal areas of evolutionary and functional divergence. Exploring protein families using existing methods such as multiple sequence alignment is computationally expensive, thus pattern search is used. However, at present, combinatorial methods of pattern search generate a large set of solutions, and probabilistic methods require richer representations. They require biological ground truth of the input sequences, such as gene name or taxonomic species, as class labels based on traditional classi fication practice to train a model for predicting unknown sequences. However, these algorithms are inherently biased by mislabelling and may not be able to reveal class characteristics in a detailed and succinct manner. A novel pattern representation called an Aligned Pattern Cluster (AP Cluster) as developed in this dissertation is compact yet rich. It captures conservations and variations of amino acids and covers more sequences with lower entropy and greatly reduces the number of patterns. AP Clusters contain statistically signi cant patterns with variations; their importance has been confi rmed by the following biological evidences: 1) Most of the discovered AP Clusters correspond to binding segments while their aligned columns correspond to binding sites as verifi ed by pFam, PROSITE, and the three-dimensional structure. 2) By compacting strong correlated functional information together, AP Clusters are able to reveal class characteristics for taxonomical classes, gene classes and other functional classes, or incorrect class labelling. 3) Co-occurrence of AP Clusters on the same homologous protein sequences are spatially close in the protein's three-dimensional structure. These results demonstrate the power and usefulness of AP Clusters. They bring in similar statistically signifi cance patterns with variation together and align them to reveal protein regional functionality, class characteristics, binding and interacting sites for the study of protein-protein and protein-drug interactions, for diff erentiation of cancer tumour types, targeted gene therapy as well as for drug target discovery.1 yea

Leveraging Auxiliary Domain Parallel Data in Intermediate Task Fine-tuning for Low-resource Translation

NMT systems trained on Pre-trained Multilingual Sequence-Sequence (PMSS) models flounder when sufficient amounts of parallel data is not available for fine-tuning. This specifically holds for languages missing/under-represented in these models. The problem gets aggravated when the data comes from different domains. In this paper, we show that intermediate-task fine-tuning (ITFT) of PMSS models is extremely beneficial for domain-specific NMT, especially when target domain data is limited/unavailable and the considered languages are missing or under-represented in the PMSS model. We quantify the domain-specific results variations using a domain-divergence test, and show that ITFT can mitigate the impact of domain divergence to some extent.Comment: Accepted for poster presentation at the Practical Machine Learning for Developing Countries (PML4DC) workshop, ICLR 202

SIB-200: A Simple, Inclusive, and Big Evaluation Dataset for Topic Classification in 200+ Languages and Dialects

Despite the progress we have recorded in the last few years in multilingual natural language processing, evaluation is typically limited to a small set of languages with available datasets which excludes a large number of low-resource languages. In this paper, we created SIB-200 -- a large-scale open-sourced benchmark dataset for topic classification in 200 languages and dialects to address the lack of evaluation dataset for Natural Language Understanding (NLU). For many of the languages covered in SIB-200, this is the first publicly available evaluation dataset for NLU. The dataset is based on Flores-200 machine translation corpus. We annotated the English portion of the dataset and extended the sentence-level annotation to the remaining 203 languages covered in the corpus. Despite the simplicity of this task, our evaluation in full-supervised setting, cross-lingual transfer setting and prompting of large language model setting show that there is still a large gap between the performance of high-resource and low-resource languages when multilingual evaluation is scaled to numerous world languages. We found that languages unseen during the pre-training of multilingual language models, under-represented language families (like Nilotic and Altantic-Congo), and languages from the regions of Africa, Americas, Oceania and South East Asia, often have the lowest performance on our topic classification dataset. We hope our dataset will encourage a more inclusive evaluation of multilingual language models on a more diverse set of languages. https://github.com/dadelani/sib-200Comment: under submissio

Revealing Subtle Functional Subgroups in Class A Scavenger Receptors by Pattern Discovery and Disentanglement of Aligned Pattern Clusters

A protein family has similar and diverse functions locally conserved as aligned sequence segments. Further discovering their association patterns could reveal subtle family subgroup characteristics. Since aligned residues associations (ARAs) in Aligned Pattern Clusters (APCs) are complex and intertwined due to entangled function, factors, and variance in the source environment, we have recently developed a novel method: Aligned Residue Association Discovery and Disentanglement (ARADD) to solve this problem. ARADD first obtains from an APC an ARA Frequency Matrix and converts it to an adjusted statistical residual vector space (SRV). It then disentangles the SRV into Principal Components (PCs) and Re-projects their vectors to a SRV to reveal succinct orthogonal AR groups. In this study, we applied ARADD to class A scavenger receptors (SR-A), a subclass of a diverse protein family binding to modified lipoproteins with diverse biological functionalities not explicitly known. Our experimental results demonstrated that ARADD can unveil subtle subgroups in sequence segments with diverse functionality and highly variable sequence lengths. We also demonstrated that the ARAs captured in a Position Weight Matrix or an APC were entangled in biological function and domain location but disentangled by ARADD to reveal different subclasses without knowing their actual occurrence positions