Gene Expression, Biological Networks, and CRISPR Systems

Vocabulary flashcards covering gene regulatory networks, molecular pathways, network topology metrics, interaction databases, and CRISPR gene-editing terminology.

Gene Expression

Overall process of converting information from genes to proteins

Complex regulation in Eukaryotes

DNA packaging, activators, interaction complexes

Gene Regulatory Networks (GRN)

Complex collection of molecular regulatory to interact with each other to control gene expression and inherently cell function

Molecular Regulators Examples

Transcription factors, microRNAs, chromatin regions

GRN Limits

Incomplete knowledge of transcription factors + epigenetic effects + miRNAs

Signal Transduction Pathways

Extracellular signals convert into specific cellular response through series of molecular events

Extracellular signal Examples

Hormones, growth factor, mitogen, stress, inflammatory cytokines

MAPK Cascade

Transmits extracellular signal to regulate gene expression, proliferation, differentiation + apoptosis

Degree

Number of connections per node

Distance

Shorted number of connection path between two nodes

Path

Sequence of connections

Reachability

Is there a path?

Closeness

Mean shorted path distance

Betweenness

How many shortest paths are there

Number of nodes

Size of Networks

Proportion of clusters

Density of network

DNA-protein Interactions

Transcription factor and methylation networks

RNA-RNA Interactions

miRNA regulatory networks

RNA-protein Interactions

Splicing regulatory networks

Protein - protein

Co-expression, co-localization, pathways, protein regulatory and signal transduction networks.

IntAct

Database system for molecular interaction

Biogrid

Database for genetic + protein interaction data for Humans and model organisms

STRING

Search tool for retrieval of interacting genes/proteins

GeneMania

Predicts gene function and functionally related genes

Pathways Commons

Collects, integrates and normalizes bio pathways and molecular interactions

Single Gene Network

Regulators and co-regulators, functional features

List of Gene Networks

Differentially expressed subnetworks, gene pathways, requires next-gen sequences

Can GRN predict?

Gene neighbors ( cluster/order), phylogenetic profiling, co-evations, mirror tree

Phylogenetic profiling

Evolutionary history, development, and relationships among groups of organism

Coexpression

2 or more genes with similar expression patterns

Omics

High throughput study of entire sets of biological molecules

Gene Level Pathways

Evaluates individual genes, variants or transcripts in isolation to test for differential expression

Pathway Level

Evaluates groups of genes, proteins, or metabolites that work together in shared biological process

Pathways

Linear or semi-linear series of molecular actions, specific cellular product

Networks

Large-scale web presenting brings/multi subreaction across the entire systems

Fixed gene set enrichment analysis

Identify prebuilt pathways or network enrichments in a set of mutated/differentially expressed genes

De Novo Network Construction Clustering

Construct specific subnetwork from set of mutated genes to identify extended list of putative cancer genes

BRAC1

Breast cancer type 1 susceptibility protein

Sorbitol

Water-soluble sugar alcohol, to increase activation of cross-talk switch

CRISPR- Cas9

Allows elective edit, cuts and modification via Cas9proteins

Cas9 NHEJ Repair

Non-homologous repair pathway leads to insertion or deletion of nucleotides to equal gene knockout

Homologous

Additions by donor DNA repair template, with new sequence flanked by homology arms lead to gene knock-in

Auxtrophic

Can't form components for growth

dCas9

Catalytically inactive Cas9 protein, can bind but not cleave

sgRNA

Single-guide to bring dCas9 to specific DNA sequence

MAD7 engineering CAS13

Uses 1 cRNA instead of cRNA + tracRBA

folA

Gene seconds for DHFR essential enzyme in folate metabolism, convert HDF to THF

THF function

Synthesis of nucleotides and cellular components

CRISPRi

dCAs9 attached to a repressor protein called KRAB, suppresses transcription and reduce gene expressions

CRIPSRa

dCAS9 attached to activating protein VOR< recruit transcription and increases expression

RNA delivery

Introduce mRNA that tells cells to produce dCas9-effector protein

RNP Delivery

Researchers introduced a ribonucleoprotein complex with dCas9 + gRNA

Electroporation

Short electric pulse creates a temporary opening in the cell membrane for molecules to enter

Transient expression

Temporary production of proteins or RNA inside host cells after introducing foreign nucleic acids without integrating the genetic material into the host cell's genome

Metastasis

Cancer cell spread from original tumor throughout the body to form new tumors

Coverage

How many cells on average represent each sgRNA in the experiment

Signal Fidelity

how faithfully a pathways’ output reflects its intended input, rather than being misinterpreted as another pathway

Signal Specificity

how selectively a ligand activates its cognitive pathway rather than a different one and how well it distinguishes between similar signals.

Gene Induction

turn on to produce RNA in response to specific internal or external stimuli

Transposon Sequence

A segment of DNA that can move to different positions within the genome, often causing mutations and altering gene expression.

Auxotrophic

genes when mutated or inactivated to render organisms unable to synthesize nutrients for growth

Monocistronic

mRNA encodes for single proteinper RNA partilce

Isoacceptor

tRNA that carries exact AA, has different anticodon to recognize synonymous codons on mRNA

Enriched

particular sgRNA becomes more abundant after experiment with the control condition.