Identification

Title

Generative and interpretable machine learning for aptamer design and analysis of in vitro sequence selection

Abstract

Selection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. We show that Restricted Boltzmann Machines (RBMs), an unsupervised two-layer neural network architecture, can successfully be trained on sequence ensembles from single rounds of SELEX experiments for thrombin aptamers. RBMs assign scores to sequences that can be directly related to their fitnesses estimated through experimental enrichment ratios. Hence, RBMs trained from sequence data at a given round can be used to predict the effects of selection at later rounds. Moreover, the parameters of the trained RBMs are interpretable and identify functional features contributing most to sequence fitness. To exploit the generative capabilities of RBMs, we introduce two different training protocols: one taking into account sequence counts, capable of identifying the few best binders, and another based on unique sequences only, generating more diverse binders. We then use RBMs model to generate novel aptamers with putative disruptive mutations or good binding properties, and validate the generated sequences with gel shift assay experiments. Finally, we compare the RBM's performance with different supervised learning approaches that include random forests and several deep neural network architectures.

Resource type

document

Resource locator

Unique resource identifier

code

https://n2t.org/ark:/85065/d73200rm

codeSpace

Dataset language

eng

Spatial reference system

code identifying the spatial reference system

Classification of spatial data and services

Topic category

geoscientificInformation

Keywords

Keyword set

keyword value

Text

originating controlled vocabulary

title

Resource Type

reference date

date type

publication

effective date

2016-01-01T00:00:00Z

Geographic location

West bounding longitude

East bounding longitude

North bounding latitude

South bounding latitude

Temporal reference

Temporal extent

Begin position

End position

Dataset reference date

date type

publication

effective date

2022-09-01T00:00:00Z

Frequency of update

Quality and validity

Lineage

Conformity

Data format

name of format

version of format

Constraints related to access and use

Constraint set

Use constraints

Limitations on public access

None

Responsible organisations

Responsible party

contact position

OpenSky Support

organisation name

UCAR/NCAR - Library

full postal address

PO Box 3000

Boulder

80307-3000

email address

opensky@ucar.edu

web address

http://opensky.ucar.edu/

name: homepage

responsible party role

pointOfContact

Metadata on metadata

Metadata point of contact