Soha Hassoun — Page 2

arXiv2020

ASAP-SML: An Antibody Sequence Analysis Pipeline Using Statistical Testing and Machine Learning

Antibodies are capable of potently and specifically binding individual antigens and, in some cases, disrupting their functions. The key challenge in generating antibody-based inhibitors is the lack of fundamental information relating sequences of antibodies to their unique properties as inhibitors. We develop a pipeline, Antibody Sequence Analysis Pipeline using Statistical testing and Machine Learning (ASAP-SML), to identify features that distinguish one set of antibody sequences from antibody sequences in a reference set. The pipeline extracts feature fingerprints from sequences. The fingerprints represent germline, CDR canonical structure, isoelectric point and frequent positional motifs. Machine learning and statistical significance testing techniques are applied to antibody sequences and extracted feature fingerprints to identify distinguishing feature values and combinations thereof. To demonstrate how it works, we applied the pipeline on sets of antibody sequences known to bind or inhibit the activities of matrix metalloproteinases (MMPs), a family of zinc-dependent enzymes that promote cancer progression and undesired inflammation under pathological conditions, against reference datasets that do not bind or inhibit MMPs. ASAP-SML identifies features and combinations of feature values found in the MMP-targeting sets that are distinct from those in the reference sets.

cs.CE↗

arXiv2020

Learning graph representations of biochemical networks and its application to enzymatic link prediction

The complete characterization of enzymatic activities between molecules remains incomplete, hindering biological engineering and limiting biological discovery. We develop in this work a technique, Enzymatic Link Prediction (ELP), for predicting the likelihood of an enzymatic transformation between two molecules. ELP models enzymatic reactions catalogued in the KEGG database as a graph. ELP is innovative over prior works in using graph embedding to learn molecular representations that capture not only molecular and enzymatic attributes but also graph connectivity. We explore both transductive (test nodes included in the training graph) and inductive (test nodes not part of the training graph) learning models. We show that ELP achieves high AUC when learning node embeddings using both graph connectivity and node attributes. Further, we show that graph embedding for predicting enzymatic links improves link prediction by 24% over fingerprint-similarity-based approaches. To emphasize the importance of graph embedding in the context of biochemical networks, we illustrate how graph embedding can also guide visualization. The code and datasets are available through https://github.com/HassounLab/ELP.

q-bio.MN↗