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# Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk

Mylène Delosière, Laurence Bernard, Catherine Hurtaud, Maxime Guilleton, Didier Viala, Andrea Rau, Muriel Bonnet, Christelle Cebo

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## To cite this version:

Mylène Delosière, Laurence Bernard, Catherine Hurtaud, Maxime Guilleton, Didier Viala, et al. Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk. Journal of Proteomics, 2023, 285, pp.104951. 10.1016/j.jprot.2023.104951. hal-04170840

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https://hal.science/hal-04170840

Submitted on 8 Sep 2023

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Distributed under a Creative Commons Attribution 4.0 International License
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# Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk

M. Delosièreª, L. Bernardª, C. Hurtaudᵇ, M. Guilletonª, D. Vialaª,ᶜ, A. Rauᵈ, M.

Bonnetª and C. Ceboᵈ

ª INRAE, Université Clermont Auvergne, Vetagro Sup, UMRH, 63122 Saint-Genes-Champanelle, France

ᵇ PEGASE, INRAE, Institut Agro, 35590, Saint-Gilles, France

ᶜ INRAE, Université Clermont Auvergne, Vetagro Sup, Metabolomic and Proteomic Exploration Facility (PFEM), 63122, Saint-Genès-Champanelle, France

ᵈ Université Paris-Saclay, INRAE, AgroParisTech, GABI, 78350, Jouy-en-Josas, France

Corresponding author:

Mylène Delosière: mylene.delosiere@inrae.fr

Dr Mylène Delosière, INRAE, Centre ARA, Site de Theix, 63122 Saint-Genès-Champanelle, France

## Acknowledgments

The authors thank APIS-GENE (https://www.apis-gene.com/) for its financial contribution to the LIPOMEC program (ANR-19-CE21-0010). Members of the IE PL experimental farm, INRAE, Dairy nutrition and physiology (IE PL, 35650 Le Rheu, France; https://doi.org/10.15454/yk9q-pf68) are acknowledged for their contribution to animal care and milk sampling. The authors thank Guy Miranda (INRAE, GABI Unit) for analyses of major milk protein fractions by LC-ESI-MS; Sylvain Emery and Arnaud Delavaud from UMR 1213 Herbivores (INRAE) for their assistance with the experiment management, sample collection and laboratory analysis; Christophe Chambon from Metabolomic and Proteomic Exploration Facility (PFEM, INRAE, Saint-Genès-Champanelle, France;

https://doi.org/10.15454/1.557239511356972E12) for analysis of the minor proteome by nano-LC-MS/MS. The authors acknowledge the support received from the
International Research Center on sustainable AgroEcosystems (6-IDEX-0001 CAP 33
20-25). 34

35

36 **Animal welfare statement**

The experiment was conducted in accordance with the French legislation on animal 37
experimentation and was approved by the French National Committee for 38
Consideration of Ethics in Animal Experimentation (Authorization: APAFiS #17944- 39
2018120416536243 v2 delivered on February 19, 2019). 40

41

42 **Conflict of interest statement**

The authors declare that they have no conflict of interest. 43

44

45 **Author ORCIDs**

Mylène Delosière: 0000-0002-8149-5070 46

Laurence Bernard: 0000-0003-1529-4243 47

Catherine Hurtaud: 0000-0002-3965-826X 48

Maxime Guilleton: 0000-0001-9963-0050 49

Didier Viala: 0000-0002-4221-9700 50

Andrea Rau: 0000-0001-6469-488X 51

Muriel Bonnet: 0000-0001-7193-3543 52

Christelle Cebo: 0000-0001-5071-9353 53

54

55 **Author's contributions :**

M. Delosière: Proteome Methodology, Statistical Methodology, Software, Data 56
curation, Formal analysis, Visualization, Writing – original draft. 57

L. Bernard: Conceptualization and management of the Lipomec project, Resources, 58
Supervision, Visualization, Writing – original draft. 59

C. Hurtaud: Conceptualization and management of the Lipomec project, Resources, 60
Data curation, Writing – review & editing. 61

M. Guilleton: Methodology, Software, Data curation, Formal analysis, Visualization, 62
Writing – original draft. 63

D. Viala: Proteome Analysis, Data Curation, Writing – review & editing. 64
65

A. Rau: Methodology, Software, Data curation, Validation, Formal analysis, Visualization, Writing – review & editing.

66

M. Bonnet: Conceptualization of the proteome methodology, conceptualization of the data analysis, data curation, Supervision, Visualization, Writing– original draft.

68

C. Cebo: Conceptualization and management of the Lipomec project, Funding acquisition, Supervision, Data curation, Visualization, Writing – original draft.

70

All authors agree to be accountable for the content of the work.

72
## Highlights

- A specific protein signature is associated with high lipolysis levels in cow milk

- CD5L and GP2 in skim milk are putative biomarkers of lipolysis

- CUL9, SURF4 and HID1 are associated with low levels of lipolysis in skim milk

- LPL inhibitors contribute to explaining low lipolysis levels observed in cow milk

## Graphical abstract

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## Abstract

Spontaneous milk lipolysis refers to the breakdown of triacylglycerols in milk.

Lipolysis impacts the organoleptic value of milk by causing off-flavours and reduces the technological properties of milk. Lipolysis is caused by lipoprotein lipase (LPL), a tightly regulated enzyme in milk. Our objective was to identify robust biomarkers of lipolysis and putative regulators of LPL enzyme in bovine milk. To achieve this goal, we used feed restriction as a lever to generate highly contrasted samples with regard to milk lipolysis. We combined statistical methods on proteomics data, milk lipolysis and LPL activity values. Following this strategy, we identified CD5L and GP2 as robust biomarkers of high lipolysis in cow milk. We also identified HID1, SURF4 and CUL9 as putative inhibitors of the lipolytic process in the milk. We thus proposed 5 putative biomarkers to be considered in future tools to manage milk lipolysis.

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## Keywords

Dairy cows, lipolysis, lipoprotein lipase, milk fat, milk proteins, biomarkers

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## Introduction

Fat is present in milk as fat globules, a supra-molecular structure made of a triglyceride core surrounded by a complex membrane called the Milk Fat Globule Membrane (MFGM). In freshly secreted milk, the MFGM is intact and forms an effective barrier that protects fat from the action of milk lipases, with an efficiency that can vary according to the molecular composition of the membrane [1]. In addition, in some cases such as agitation, pumping or homogenization of milk, this membrane is damaged and lipases are able to reach the triglyceride core causing lipolysis [2].

Milk lipolysis, that is, enzymatic degradation of milk triglycerides into free fatty acids by the lipoprotein lipase (LPL; EC:3.1.1.34), severely impairs milk quality from both the organoleptic and the technological points of view. Off-flavours originating from free fatty acids and their oxidation products in milk are not appreciated by consumers. Moreover, the presence of partial triglycerides in milk impairs its technological properties, like foaming and creaming abilities [3]. Controlling milk lipolysis is therefore an economic issue for dairy producers.

Spontaneous lipolysis of milk results from a complex interplay between farming practices, animal physiology and animal genetics [4,5], but underlying mechanisms
are still poorly understood. At the molecular level, the lipolytic system is constituted by the lipoprotein lipase, cofactors (activators and inhibitors) and substrate (milk triglycerides), and the resulting products are free fatty acids and partial glycerides. In the native bovine milk, the skim fraction is the richest source of LPL mainly associated with the casein micelle through electrostatic interactions [3] and upon cooling the proportion of LPL linked to the MFGM increases [6,7]. Inactive LPL can refold into active LPL dimers in the presence of calcium ions and this phenomenon is potentiated by the presence of activators, namely serum albumin, lipoproteins, heparin or glycerol [8], which are mainly located in skim milk. The presence of LPL inhibitors has also been documented in milk. A component of the milk proteose-peptone fraction PP3, also known as lactophorin, has been identified as a potential LPL inhibitor [9]. The skim milk proteose-peptone component 5 (PP5, residues 1–105 and 1–107 of β-casein) has been identified in some studies as an activator of LPL [10] and in other studies, as an inhibitor of LPL [9]. However, most of these studies dealing with the identification of milk and skim milk lipase activity regulators were conducted in the 1980s [9, 11–13] and need to be reassessed in view of the major advances in proteomics that have occurred over the past decade, especially with regard to the analysis of milk protein fractions [14,15].

The aim of the present study is to discover biomarkers of lipolysis in skim milk by using a model of feed restriction as a lever to produce milk samples with contrasted lipolysis rates [16]. To achieve this outcome, we combined statistical methods on our proteomics data with milk lipolysis values and LPL enzyme activities to identify robustly discriminant proteins of lipolysis in milk. Following this strategy, we further describe the protein signatures of spontaneous lipolysis or LPL activity in skim milk. We acknowledge some limitations in our approach. In order to perform satisfactory proteomic analysis of skim milk, milk fat was removed with skimming, but part of the LPL is located in the fat phase. However, our results help to better understand the biological mechanisms of milk fat degradation through the identification of putative regulators of lipase activity in milk, which is a prerequisite to design a test to detect lipolysis in milk samples.

# 1. Material and methods
## 1.1 Animals and experimental design

The experiment was conducted at the Installation Expérimentale Production Laitière, INRAE, Dairy nutrition and physiology (IE PL, 35650 Le Rheu, France; https://doi.org/10.15454/yk9q-pf68) with agreement for animal housing number C-35-275-23. This study was realized on samples from sixteen primiparous and multiparous Holstein cows at 156 ± 20 days in milk fed with diet treatments based on corn silage and differing by the level of feeding. These cows are a subsample of the 44 cows included in a reverse design on feeding level during 4 weeks split into 2 two-week periods in March 2019 [16]. Two feeding levels were considered: “non-restricted”, with cows fed a corn silage-based diet at 100% of ad libitum dry matter intake (DMI), and “restricted”, corresponding to a corn silage-based diet at 65% of ad libitum DMI. For omics studies, 8 cows in each two-week period were used. During period 1, each group of cows first received the non-restricted diet, followed by the restricted diet. During period 2, the order of feeding levels was reversed. Further details about the feed offered in the two diets can be found in [16]. The animals had access to fresh water *ad libitum*.

## 1.2 Milk processing and lipolysis determination

The milk yields of individual animals were recorded over 6 milkings at 8:00 and 16:30 each week. Milk samples were collected individually on morning milking on the last day of each experimental period, with one part immediately treated with bronopol-B2 preservative (LIAL, Aurillac, France) to measure fat, protein and lactose content (MyLab, Chateaugiron, France). The other part of milk (unpreserved) was used to determine the milk lipolysis level using the copper soap method (mEq/100g fat) [5,17] as described in detail in [16]. The morning lipolysis levels of milk collected on the last day of the period were used to define groups of low and high lipolysis cows based on a threshold of 0.5 mEq/100 g fat: Low Lipolysis (LL group with mean of 0.32 ± 0.12 mEq/100 g fat) vs High Lipolysis (HL group, 0.84 ± 0.33 mEq/100 g fat). Unpreserved milk was also stored at -80°C for protein extraction and identification analyses and LPL activity determination (nmol/mn/ml) measured in vitro using a radiolabelled substrate [18].

## 1.3 Major protein identification using LC-ESI-MS

Major milk proteins, namely the four caseins (αs1-caseins, αs2 caseins, β-caseins and κ-caseins), α-lactalbumin, and β-lactoglobulin and all their isoforms were
identified and quantified using our improved method combining reverse-phase high performance liquid chromatography (Ultimate LC 3000 system, Thermo Fisher Scientific, Waltham, MA) with an ESI-TOF mass spectrometer micrOTOF II focus (Bruker Daltonics, Wissembourg, France) [19]. Briefly, milk samples were placed on dry ice immediately after milking and stored at -80°C for further analyses. Milk samples were rapidly thawed at 37°C then skimmed by centrifugation at 2 000 g and 4°C for 10 min. The cream was removed by means of a spatula and the skimmed milk was aliquoted into fractions of 20 and 100 µL, frozen at -20°C and kept under these conditions until analysis by Liquid Chromatography-Electro Spray Ionization-Mass Spectrometry (LC-ESI-MS). Identification of the main milk protein isoforms was performed using our in-house mass database of bovine milk proteins containing nearly 3 000 theoretical masses, corresponding to the multiple isoforms of milk proteins including genetic and splicing variants, post-translationally modified proteins (phosphorylated and glycosylated) and main known plasmin hydrolysis products.

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## 1.4 Minor protein identification using nano-LC-MS/MS

### 1.4.1 Skim milk protein isolation, concentration and digestion

All reagents were purchased from Sigma-Aldrich (Saint Louis (MO)) except when otherwise specified. The raw milk was slightly defrosted during one night at 4°C and milk components equilibrated by incubation during 1 h at 37°C. The equilibrated raw milk was centrifuged at 3 500 g for 15 min at 4°C to separate the cream from the skimmed milk (SM). Acetic acid was added to the SM reaching pH 4.6 to precipitate the caseins. The homogenate was centrifuged at 10 000 g for 10 min at 4°C to discard caseins and supernatant recovered until protein concentration determination. Enrichment of minor or low-abundance SM proteins was performed using the ProteoMiner Small-Capacity columns (#163-3006, Bio-Rad Laboratories, Hercule (CA)) according to the manufacturer's instructions. Column was washed twice, and 10 mg of proteins from SM were deposited on column and incubated 2 h at room temperature (RT) under agitation. Then, spin columns were washed with buffer twice and with purified milli-Q water once (1 min at RT) followed by a 1 000 g centrifugation in order to eliminate unbound proteins. Proteins enriched from medium- and low-abundance were incubated for two runs of 15 min in 20 µL of elution buffer (RT) and centrifuged at 1 000 g. Supernatant was recovered until protein concentration

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determination using Pierce™ BCA protein assay kit (Fisher Scientific, Hampton (NH)).

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Twenty µg of proteins were mixed with reducing sodium dodecylsulfate buffer (4%) with dithiothreitol (20 mM) and incubated 10 min boiling in order to reduce disulphide bonds. Then proteins were alkylated in iodoacetamide (50 mM) during 45 min protected from light. After acidification with phosphoric acid (1.2%), S-Trap® buffer (triethylammonium bicarbonate 100 mM; in ethanol 90%) was added and proteins were deposit on S-Trap® column (Protifi, Fairport, NY). Columns containing proteins were centrifuged at 4 000 g during 10 min, washed with S-Trap® buffer and this step was repeated 3 times.

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SM protein digestion was performed with sequencing grade trypsin (Promega, Madison (WI)) 1:50 [w/w] enzyme/protein ratio in triethylammonium bicarbonate (50 mM) with overnight incubation at 37°C. Tryptic peptides were extracted by adding 60 µL of 0.2% formic acid in acetonitrile (50%) followed by centrifugation at 4 000 g during 10 min repeated twice. Supernatants containing peptides were dried by SpeedVac vacuum concentrator (ThermoScientific, Illkirch (FR)). Peptides were recovered in 100 µL of 5% acetonitrile and 0.05% trifluoroacetic acid (TFA) solution with sonication during 5 min and transferred into glass vials (Interchim, Montluçon (FR)) prior to nano-LC-MS/MS analysis.

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### 1.4.2 Peptide analysis on nano-LC-MS/MS

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Peptide mixtures were analysed by nano-LC-MS/MS using an Ultimate 3 000 system coupled to a QExactive HF-X mass spectrometer (MS) (Thermo Fisher Scientific). A volume of 6 µl of peptide extract was first concentrated and desalted at a flow rate of 30 µl/min on a C18 pre-column 5 cm length x 100 µm (Acclaim PepMap 100 C18, 5 µm, 100A nanoViper) equilibrated with Trifluoroacetic Acid 0.05% in water. Then this preconcentration column was switched online with a nanoflow analytical C18 column (Acclaim PepMap 100 - 75 µm inner diameter x 25 cm length; C18 - 3 µm -100Å - SN 10719167) equilibrated at a flow rate of 300 nL/min with a 95% solvent A (99.9% H2O, 0.1% formic acid). The peptides were separated according to their hydrophobicity using a gradient of solvent B (99.9% acetonitrile, 0.1% formic acid) from 5 to 32% during 50 min. For MS analysis, eluted peptides were electrosprayed in positive-ion mode at 1.6 kV through a nanoelectrospray ion source heated to 250°C. The MS operated in data dependent mode: the parent ion was selected in the
orbitrap cell (FTMS) at a resolution of 120 000 and each MS analysis was followed by 167 168

At the end of the LC-MS/MS analysis, the raw data processing of peptide MS/MS 169 spectra was carried out with Progenesis QI software (version 4.2, Nonlinear 170 Dynamics, Newcastle upon Tyne, UK). The software defined a reference run used to 171 perform an automatic alignment of all other runs considering a maximum allowable 172 ion charged set to 5. The detected ions were grouped in a file (mgf) directly exported 173 to the Mascot v2.5 (http://www.matrixscience.com) interrogation engine and searched 174 against a *Bos taurus* decoy database (i.e. ref_bos_taurus, 37 513 sequences) with 175 the following parameters during the request: precursor mass tolerance of 10 ppm and 176 fragment mass tolerance of 0.05 Da, a maximum of two missed cleavage sites of 177 trypsin, carbamidomethylation (C), oxidation (M) and deamidation (NQ) set as 178 variable modifications. Protein identification was validated when at least two peptides 179 from one protein showed statistically significant identity above Mascot scores with a 180 false discovery rate (FDR) of 1%. For label-free protein quantification analysis, the 181 identified peptides from the database search were imported back to Progenesis QI 182 software. All unique validated peptides of an identified protein were included and the 183 total cumulative abundance was calculated by summing the abundances of all 184 peptides allocated to the respective protein. Consequently, proteins were quantified 185 based on the intensities of the specific validated peptides. 186

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1.5 Statistical analysis 188

Statistical analyses were performed using R (version 4.2.1). All data came from 2 189 groups of 8 animals forming a part of the reverse design experiment (full details in 190 Hurtaud et al., 2023). As cited earlier, the milk lipolysis level was used to constitute 191 the Low Lipolysis (LL) group with a mean of 0.32 ± 0.12 mEq/100 g fat and the High 192 Lipolysis (HL) group with a mean of 0.84 ± 0.33 mEq/100 g fat. Thus, the 193 experimental design consists of the following fixed effects: period (P1 vs P2, differing 194 by 15 d of lactation), sequence (order of feed restriction treatment), and lipolysis level 195 (LL vs HL). We note that as both diets (restricted and unrestricted) were fed in 196 succession to each cow, repeated measurements were available for each cow in this 197 design. 198
Animal parameters (such as DMI, milk production and composition) and major proteins from milk containing 0.3% missing variables were imputed by the k-nearest neighbour method (k=5) using the impute package (version 1.70.0).

A linear mixed model with fixed effects (period, sequence and lipolysis) and a random animal effect was fit for animal parameters using the lme4 package (version 1.1.31), and statistical significance was evaluated using Type II sums of squares in the Anova function from the car package (version 3.1.1; p < 0.05). The sequence effect was not significant and was thus removed from the model.

Raw minor protein abundances from SM containing 0.4% missing variables were imputed by the k-nearest neighbour method (k=5) using the impute package.

Abundances were then log-transformed. We applied two complementary statistical analyses to identify a proteomic signature that discriminates the LL and HL groups: i) a parametric univariate differential analysis (Diff-A) to identify significant proteins one by one based on their abundances; and to go further ii) a sparse multi-level multivariate analysis to identify a concise signature of proteins strongly linked to either lipolysis (sPLS-lipolysis) or LPL activity (sPLS-LPL-activity). The parametric univariate differential analysis (Diff-A) was performed by fitting to each protein an empirical Bayes linear model including lipolysis, sequence and period fixed effects and a random animal effect using the limma package (version 3.52.2). As no significant effect was observed across proteins for period and sequence, these were removed from the model. P-values were adjusted to control the FDR (adj.P.Val) using the Benjamini-Hochberg approach. Statistical significance was considered at adj.P.Val < 0.1 and an absolute fold change threshold of 1.5.

Sparse multi-level partial least square analyses (sPLS) were performed in regression mode with paired observations on cows using the mixOmics package (version 6.20.0, Rohart et al., 2017). Predictor variables (X) corresponded to the log protein abundances, and the response variable (Y) to either the milk lipolysis (sPLS-lipolysis) or the milk LPL activity (sPLS-LPL-activity). For each sPLS model, we retained 2 components, both including a total of 30 proteins with non-zero loadings. A posteriori, the first sPLS component for each model was found to be highly discriminative between the LL and HL groups. The proteins with non-zero loadings in the first component were compiled into lists of milk lipolysis related proteins and LPL activity related proteins with their respective contributions. Contributions correspond to the
232 weight assigned to each protein to define each component; larger absolute values
233 mean that a given protein has a greater importance for a given component.

234 Lists of proteins were mined for biological meaning by a gene ontology (GO)
235 enrichment analysis, performed using the ProteINSIDE webservice online tool
236 version 2.0 (available at https://umrh-

237 bioinfo.clermont.inrae.fr/ProteINSIDE_2/index.php?page=upload.php, [20]) based on
238 *Bos taurus* and a search of biological reactions on Reactome based on *Homo
239 sapiens*.

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## 2. Results
---

### 2.1 Highly contrasted milk samples with regard to spontaneous lipolysis levels
---

243 We used feed restriction of the cows as a lever to generate two groups of 8 cows with
244 contrasted milk in terms of lipolysis levels for use in omics studies. The performance
245 data of these 8 dairy cows were comparable with those on the full set of 44 cows in
246 the original study [16].

247 The parameters relative to the ingestion of the 8 dairy cows from the LL group (fed an
248 unrestricted diet) and the HL group (fed a restricted diet) are reported in
249 Supplementary Table S1. As expected, the milk yield and composition are
250 dramatically divergent between LL and HL groups (Table 1). The milk production
251 decreased by 9.7% in the HL compared with LL group (P<0.05). The total milk
252 protein content was reduced by 16.7% in the HL group compared to the LL group
253 (583.4 g and 486.1 g secreted in morning milk, respectively). Both the casein and
254 soluble protein content were divergent between LL and HL groups (-6.5% and -9.6%,
255 respectively). At the same time, milk lipolysis increased by a factor of 2.6 in the HL
group compared with the LL group (P<0.05). Interestingly, the milk LPL activity
256 increased by a factor of only 1.4 in the HL group (P<0.05). Although the correlation
257 between LPL activity and lipolysis in milk is high (r=0.69; P = 0.003; Figure 1), the
258 increase in the milk LPL activity (+44.5%) cannot solely explain the dramatic increase
259 in lipolysis levels we observed in the HL group (+162.5%), thus suggesting that
260 regulators may amplify the lipolytic response in milk.

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### 2.2 Spontaneous lipolysis modulates the abundances of skimmed milk proteins
---

263 635 proteins were identified in our study and raw abundances for each protein are
264 reported in Supplementary Table S3. Among these 635 proteins, the spontaneous
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lipolysis significantly impacts the milk abundances of eight proteins. The volcano plot (Figure 2), resulting from the parametric univariate analysis, displays the seven proteins with higher abundance (A0A3Q1M3L6, CD5L, A0A3Q1LRW4, KRT10, GP2, APOA4, LBP) and the one with lower abundance (CUL9) in the HL compared with LL group (Table 2). Interestingly, the LPL protein (P11151) was 1.9 times more abundant in HL compared with LL group, but this increase was not statistically significant.

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## 2.3 Milk protein signature of lipolysis in milk

The sPLS multivariate analysis of milk lipolysis (Y) and log protein abundances (X) reveals a component that is highly discriminative between the HL and LL groups (Supplementary Figure S1). The corresponding milk proteins implicated in lipolysis are reported in Table 3. Among the 15 proteins associated with the HL group, the ten with the largest weights corresponded to two caseins (CSN1S2, CSN1S1), 3 apolipoproteins (APOE, APOA4, APOA1), CD5L, LBP, A0A3Q1LRW4, CNTFR and GP2. Among the 15 proteins associated with the LL group, the ten with the largest weights are ALOX15, SDHA, FASN, GNG12, SURF4, STK38, HID1, ABCG2, MYO6 and UQCRC2 (Table 3).

The 15 proteins associated with HL are annotated by terms within the biological process (BP) ontology related to the "positive regulation of cholesterol esterification", the "steroid esterification" and the "very-low-density lipoprotein particle remodelling" for APOA1, APOA4 and APOE (Supplementary Table S3). Similarly, the 15 proteins associated with the LL group were annotated by terms within the BP ontology highlighting the "positive regulation of protein lipidation" and "lipoprotein metabolic process" and the "establishment of protein localization at the membrane of reticulum endoplasmic" for both RAB3GAP1 and RAB3GAP2 (Supplementary Table S3).

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## 2.4 Milk protein signature of LPL activity

The first component of the sPLS multivariate analysis of milk LPL activity (Y) and log protein abundances (X) similarly discriminated between the HL and LL groups (Supplementary Figure S2). SM proteins related to the level of milk LPL activity are listed in Table 4. Seventeen proteins were strongly associated with the HL group (i.e., positive loadings for component 1 of the sPLS) with GP2, BSPRY, KRT10, ANXA7, MARCKS, CD5L, SLC5A9, SLC6A8, A0A3Q1M3L6 and IDH1 in the top 10. Among

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the 13 proteins associated with the LL group, HID1, SQLE, CUL9, VAT1, PHB2, ACSL3, NDRG4, ATP13A3, FASN and ANKRD13A were in the top 10 (Table 4).

The 17 proteins associated with HL were significantly annotated by terms within the BP category that emphasized “localization” for CD5L, GP2, NAPA, SH3GLB1, SLC5A9, SLC6A8, the “negative regulation of cholesterol metabolic process” for ERLIN2 the “isocitrate metabolic process”, the “glyoxylate cycle” and “tricarboxylic acid metabolic process” for IDH1. Moreover, 13 proteins among the 17 were annotated by the “membrane” term within the CC category (Supplementary Table S3).

The 13 proteins associated with the LL group were annotated by terms within the BP category that highlight the “regulation of phospholipid metabolic process”, particularly phosphatidylcholine, for ACSL3 and PHB2 and “negative regulation of protein localization to endosome” for ANKRD13A (Supplementary Table S3).

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## 2.5 Putative milk biomarkers of milk lipolysis

Crossing the protein lists resulting from the univariate and multivariate statistical analyses highlights the CD5 molecule like (CD5L) and the Glycoprotein 2 (GP2).

These are therefore putative biomarkers of high lipolysis in milk (Figure 3). CD5L and GP2 skim milk abundances correlated positively with milk lipolysis (r = 0.69; P = 0.003 and r = 0.5; P = 0.04) and milk LPL activity (r = 0.68; P = 0.003 and r = 0.6; P = 0.01) (Supplementary Table S4).

Focusing on protein lists associated with the LL group, the Surfeit locus protein 4 (SURF4) and Chromosome 17 open reading frame 28 ortholog (HID1) are common proteins linked to milk lipolysis (sPLS-lipolysis) and milk LPL activity (sPLS-LPL activity) (Figure 4). SURF4, HID1 and CUL9 are negatively correlated with both lipolysis (r = -0.63, P = 0.008; r = -0.4, P = 0.1 and r = -0.48, P = 0.06) and LPL activity in milk (r = -0.74, P = 0.0009; r = -0.6, P = 0.01 and r = -0.59, P = 0.01) (Supplementary Table S4). These proteins are therefore good candidates that may be indicative of low lipolysis in the milk of dairy cows.

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# 3. Discussion

As expected, the feed restriction of dairy cows dramatically induced lipolysis in milk (+162.5%; HL group) compared with cows fed with normal diet (LL group) [16,21].

332
333 Noticeably, while lipolysis increased 2.6 times in the HL compared to LL group, the activity of the LPL enzyme only increased 1.4 times, thus suggesting that molecules 334 may act as regulators of the enzyme in skim milk (Table 1). However, the LPL activity 335 measured in vitro in optimal conditions represents the potential LPL activity and not 336 the in vivo activity. Furthermore, previous studies in cows showed that milk lipolysis 337 was poorly correlated to LPL activity [22], which is probably due at least in part to the 338 major cellular location of the LPL in the casein micelle fraction of milk in cows. These 339 considerations support giving more weight to the molecules identified as a signature 340 of lipolysis within the skim milk. 341

342 The feed restriction necessarily impacts the milk proteome [21,23]. Our aim was to 343 identify robust biomarkers of milk lipolysis and a list of putative regulators of lipolysis 344 in skim milk to better understand the lipolytic processes. To achieve this goal, we first 345 performed a classical univariate statistical analysis on our proteomics data to identify 346 differentially abundant proteins between lipolysis treatments while accounting for 347 other experimental factors. We then performed two multivariate statistical analyses 348 on the proteomics abundance data to identify proteins forming signatures of lipolysis 349 and milk LPL enzyme activity. sPLS is a powerful tool that seeks to maximize the 350 covariance between the proteomic abundances and response variable of interest 351 (lipolysis, LPL activity) using a set of latent components, where a lasso penalization 352 is used to focus interest on a concise set of predictive biomarkers. Finally, we 353 compared differential proteins and those forming signatures of lipolysis and LPL 354 activity to identify proteins involved in the regulation of the lipolytic process in milk. 355 Following this 3-step strategy, we identified CD5L and GP2 as robust biomarkers and 356 putative regulators of lipolysis in milk (Figure 3). These proteins were consistently 357 identified in the differential analysis, as well as sPLS-lipolysis and sPLS-LPL activity 358 analyses, highlighting them as key molecules involved in the lipolytic pathway in 359 bovine milk. CD5L, also called Apoptosis inhibitor of macrophage (AIM) or apoptosis 360 inhibitor 6 (Api6), is a soluble member of the scavenger receptor cysteine-rich 361 superfamily, which is secreted by mature tissue macrophages in mouse in the 362 context of inflammation and obesity. Kurokawa et al. [24,25] reported that the 363 AIM/Api6/CD5L protein is incorporated into adipocytes via CD36-mediated 364 endocytosis, and induces lipolysis by suppressing the activity of fatty acid synthase 365 (FASN). In our study, CD5L negatively correlates (r = -0.75; P = 0.0007) with FASN, 366 the latter of which was strongly associated with the LL group for both sPLS-lipolysis
and sPLS-LPL-activity (Tables 3 and 4). As proposed earlier by Iwamura et al. [26] in adipocytes of mice, we further suggest that in bovine mammary epithelial cells, the highly abundant CD5L binds to cytosolic FASN, inhibiting its enzymatic activity and thus lowering the milk short and medium chain FA from *de novo* mammary synthesis. In other words, CD5L may act by repressing *de novo* synthesis by FASN, favouring a higher fatty acid uptake by both the mammary LPL and NEFA transporters for milk lipid synthesis [27]. The latter being favoured by the high plasma NEFA concentration observed due to adipose mobilization which was associated with lipolysis in milk [21]. GP2 was identified in the heat- and acid-stable fraction of ovine milk [28] and was recently listed in all the fractions of bovine milk throughout lactation [15]. The heat- and acid-stable fraction of bovine milk belongs to the proteose-peptone fraction, which contain potential activators or inhibitors of LPL enzyme [29]. Most of the component of proteose-peptone fraction are fragments of caseins produced by the action of endogenous plasmin and the main constituents are recognized as components 3, 5, 8 [30,31]. Peptone protease (PP) 5 have been identified both as an activator [10] or an inhibitor of LPL enzyme [9,21] and remain controversial. Among this PP fraction, the potential GP2 role in the lipolysis process has not been yet addressed. However, given its structure of glycosylphosphatidylinositol-anchored glycoprotein, GP2 may be involved in the link of LPL with the MFGM. This hypothesis remains to be investigated and is based on the observations that glycosylphosphatidylinositol-anchored glycoprotein such as GPIHBP1 is involved in the binding of LPL and chylomicrons in mice [32]. Moreover, GP2 is highly positively correlated with the glypican-1 protein (GPC1) in an sPLS discriminant analysis between the LL and HL groups (Supplementary Figure S3 reports the circle plot of component 1 and 2). GPC1 is a cell surface proteoglycan carrying an heparan sulfate moiety, which facilitates or inhibits the interaction of proteins with lipid-rafts. Heparin-like glycosaminoglycans have been identified as potential activators of LPL [29,33]. Among research focusing on the interactions between LPL and MFGM allowing its access to its substrates, LPL is known to bind to heparan sulfate-type glycosaminoglycans present on the surface of MFG [6]. All these assumptions justify analyzing the involvement of GP2 in the localization of LPL close to its substrate, supported by GP2 positive correlation with milk LPL activity (r = 0.60; P = 0.01) (Supplementary Table S4).
Three proteins were both differentially abundant and related to lipolysis. APOA4, A0A3Q1LRW4 and LBP were identified in the milk from the HL group as strongly associated proteins (Table 3, Figure 3). APOA4 is a known actor in lipolysis, since it is required for efficient activation of LPL by APOC-II [3,34]. A0A3Q1LRW4 protein is an immunoglobulin fragment, but not well described. Lastly, the LBP protein addressing the HL group indicates modification of the immune response and lipid transport in the cows in line with adaptive response to feed restriction [35].

Dairy cows fed diets covering requirements present low lipolysis levels in milk despite the presence of LPL, thus suggesting that the LPL enzyme is tightly regulated. It is therefore of interest to identify not only proteins associated with high levels of lipolysis in milk, but also proteins associated with low levels of lipolysis, the latter of which may be putative inhibitors of lipolysis in milk. The cullin 9 protein (CUL9) was identified in the milk of the LL group both in our differential analysis and sPLS-LPL activity analysis (Figure 4). CUL9 belongs to the cullin family of proteins, molecular scaffolds that have crucial roles in the homeostasis of cellular proteins through the ubiquitin-proteasome system [36]. Cullins work in concert with RING proteins as docking proteins to add ubiquitin to specific proteins, targeting them for destruction. Such a regulation of lipase activity through ubiquitination has been recently demonstrated for the adipose triglyceride lipase in hepatic cells [37].

Two additional proteins were strongly associated with reduced lipolysis levels in milk: SURF4 (Surfeit locus protein 4) and HID1 (Chromosome 17 open reading frame 28 ortholog protein) (Figure 4). SURF4 is an endoplasmic reticulum (ER) cargo receptor that mediates the selective export of lipoproteins to facilitate their secretion, thus playing a crucial role for the maintenance of lipid homeostasis [38].

As well as SURF4, HID1 protein is associated with low levels of LPL activity and lipolysis (Figure 4). HID-1 controls formation of large dense core vesicles by influencing cargo sorting of neuropeptides and peptide hormones through acidification of the trans Golgi network [39]. HID1 is thus involved in the release of insulin by pancreatic cells through the processing of proinsulin to functionally active hormone [40]. Moreover, in our study, the expression of HID1 is positively correlated with the expression of FASN in the LL group ($r = 0.72$; $P = 0.001$; Supplementary Table S4), thus favouring the mammary de novo FA pathway in the case of a sufficient feeding level.
## 4. Conclusions

In this study, we used feed restriction as a lever to produce highly contrasted samples with regard to lipolysis levels in bovine milk. Following proteomic studies, we combined uni- and multivariate statistical analyses with milk lipolysis values and/or LPL enzyme activities measured in milk to identify key regulators of lipolysis in bovine milk. We identified the CD5L and GP2 proteins as robust biomarkers of high lipolysis in cow milk. HID1, SURF4 and CUL9 are putative inhibitors of the lipolytic process in the milk. The data provided here constitute a robust basis for further tests on a larger population to design a quick on-farm diagnosis tool such as strip tests to monitor lipolysis levels in cow milk.

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<table><caption>Table 1: Morning milk parameters in LL and HL groups.</caption><thead><tr><th></th><th>LL</th><th>HL</th><th>SEM</th><th>p-val<br>lipolysis</th><th>Significance of<br>lipolysis</th><th>Significance of<br>period</th></tr></thead><tbody><tr><td colspan="7"><strong>Milk yield and gross composition</strong></td></tr><tr><td>Milk yield (kg)</td><td>18.5</td><td>16.7</td><td>0.62</td><td>0.031</td><td>*</td><td>NS</td></tr><tr><td>Milk fat content (g secreted)</td><td>710.7</td><td>611.5</td><td>31.8</td><td>0.056</td><td>NS</td><td>NS</td></tr><tr><td>Milk protein content (g secreted)</td><td>583.4</td><td>486.1</td><td>24.2</td><td>0.0004</td><td>***</td><td>NS</td></tr><tr><td>Milk lactose content (g secreted)</td><td>908.1</td><td>825.3</td><td>31</td><td>0.044</td><td>*</td><td>NS</td></tr><tr><td>Somatic Cell Count (x10<sup>3</sup>/mL)</td><td>34.3</td><td>33.5</td><td>8</td><td>0.967</td><td>NS</td><td>NS</td></tr><tr><td colspan="7"><strong>Milk fat characteristics</strong></td></tr><tr><td>Lipolysis (mEq/100g fat)</td><td>0.32</td><td>0.84</td><td>0.09</td><td>0.002</td><td>**</td><td>NS</td></tr><tr><td>Lipoprotein Lipase activity<br>(nmol/min/ml)</td><td>514.8</td><td>744.2</td><td>35.7</td><td>0.002</td><td>**</td><td>NS</td></tr><tr><td>Milk fat globule diameter (d<sub>4,3</sub><sup>*</sup>) (µm)</td><td>3.74</td><td>3.65</td><td>0.09</td><td>0.587</td><td>NS</td><td>NS</td></tr><tr><td>Milk fat globule diameter (d<sub>3,2</sub><sup>*</sup>) (µm)</td><td>3.31</td><td>3.13</td><td>0.07</td><td>0.185</td><td>NS</td><td>NS</td></tr><tr><td>Milk fat globule area (S<sup>*</sup>) (m<sup>2</sup>)</td><td>1.97</td><td>2.11</td><td>0.05</td><td>0.147</td><td>NS</td><td>NS</td></tr><tr><td colspan="7"><strong>Milk proteins characteristics</strong></td></tr><tr><td>Protein content (g/kg)</td><td>31.2</td><td>29</td><td>0.5</td><td>0.011</td><td>*</td><td>NS</td></tr><tr><td>Nitrogen content (g/kg)</td><td>32.5</td><td>30.3</td><td>0.5</td><td>0.01</td><td>**</td><td>NS</td></tr><tr><td>Non-casein nitrogen (g/kg)</td><td>6.4</td><td>6</td><td>0.1</td><td>0.046</td><td>*</td><td>*</td></tr><tr><td>Non-protein nitrogen (g/kg)</td><td>1.25</td><td>1.32</td><td>0.04</td><td>0.215</td><td>NS</td><td>NS</td></tr><tr><td>Casein content (g/kg)</td><td>26</td><td>24.3</td><td>0.5</td><td>0.008</td><td>**</td><td>NS</td></tr><tr><td>Soluble protein content (g/kg)</td><td>5.2</td><td>4.7</td><td>0.2</td><td>0.011</td><td>*</td><td>NS</td></tr><tr><td>Casein/protein ratio (%)</td><td>82.8</td><td>83.6</td><td>0.5</td><td>0.054</td><td>NS</td><td>NS</td></tr></tbody></table>

<footnote>*d<sub>4,3</sub> = Σ(N<sub>i</sub>×d<sub>i</sub><sup>4</sup>)/Σ(N<sub>i</sub>×d<sub>i</sub><sup>3</sup>)</footnote>

<footnote>*d<sub>3,2</sub> = Σ(N<sub>i</sub>×d<sub>i</sub><sup>3</sup>)/Σ(N<sub>i</sub>×d<sub>i</sub><sup>2</sup>)</footnote>

<footnote>*S = 6/(ρ × d<sub>3,2</sub>) (with N<sub>i</sub> the number of MFG in diameter class d<sub>i</sub> and ρ the density of the particle considered (0.92 for fat))</footnote>

<footnote>P-values were significant at <0.001 (**); <0.01 (***) and <0.05 (*)</footnote>

<footnote>NS = not significant</footnote>
<table><caption>Table 2: Differentially regulated proteins in HL group compared with LL group from the parametric univariate differential analysis (Diff-A).</caption><thead><tr><th>Accession</th><th>Gene name</th><th>Protein name</th><th>Raw abundance ratio (HL/LL)</th><th>FC</th><th>RSD</th><th>Adjusted-Pvalue</th></tr></thead><tbody><tr><td>A0A3Q1M3 L6</td><td>Uncharacterized protein</td><td>Immunoglobulin heavy constant mu</td><td>2.0</td><td>1.6</td><td>0.262</td><td>0.078</td></tr><tr><td>A6QNW7</td><td>CD5L</td><td>CD5 molecule like</td><td>3.1</td><td>2.2</td><td>0.624</td><td>0.078</td></tr><tr><td>A0A3Q1LR W4</td><td>Uncharacterized protein</td><td>Immunoglobulin heavy constant mu</td><td>2.7</td><td>1.9</td><td>0.470</td><td>0.078</td></tr><tr><td>P06394</td><td>KRT10</td><td>Keratin, type I cytoskeletal 10</td><td>2.7</td><td>2.1</td><td>0.590</td><td>0.078</td></tr><tr><td>A0A3Q1M1 93</td><td>GP2</td><td>Glycoprotein 2</td><td>2.1</td><td>1.7</td><td>0.315</td><td>0.078</td></tr><tr><td>Q32PJ2</td><td>APOA4</td><td>Apolipoprotein A-IV</td><td>5.6</td><td>2.9</td><td>0.739</td><td>0.078</td></tr><tr><td>Q2TBI0</td><td>LBP</td><td>Lipopolysaccharide-binding protein</td><td>2.6</td><td>1.9</td><td>0.521</td><td>0.080</td></tr><tr><td>E1BM39</td><td>CUL9</td><td>Cullin 9</td><td>0.3</td><td>-2.4</td><td>0.760</td><td>0.099</td></tr></tbody></table>
<table><caption>Table 3: List of 30 proteins from component 1 of sparse multi-level multivariate analysis (sPLS – milk lipolysis) contributing to LL or HL group</caption><thead><tr><th rowspan="2">Accession</th><th rowspan="2">Gene Name</th><th rowspan="2">Protein Name</th><th colspan="2">Importance of contribution to comp1</th></tr><tr><th>HL</th><th>LL</th></tr></thead><tbody><tr><td>P02663</td><td>CSN1S2</td><td>Alpha-S2-casein</td><td>0.338</td><td>.</td></tr><tr><td>Q03247</td><td>APOE</td><td>Apolipoprotein E</td><td>0.314</td><td>.</td></tr><tr><td>A6QNW7</td><td>CD5L</td><td>CD5 molecule like</td><td>0.313</td><td>.</td></tr><tr><td>Q2TBI0</td><td>LBP</td><td>Lipopolysaccharide-binding protein</td><td>0.242</td><td>.</td></tr><tr><td>P02662</td><td>CSN1S1</td><td>Alpha-S1-casein</td><td>0.231</td><td>.</td></tr><tr><td>A0A3Q1LRW4</td><td>Uncharacterized protein</td><td>Immunoglobulin heavy constant mu</td><td>0.192</td><td>.</td></tr><tr><td>Q32PJ2</td><td>APOA4</td><td>Apolipoprotein A-IV</td><td>0.140</td><td>.</td></tr><tr><td>P15497</td><td>APOA1</td><td>Apolipoprotein A-I</td><td>0.133</td><td>.</td></tr><tr><td>A0A3Q1LQY1</td><td>CNTFR</td><td>Ciliary neurotrophic factor receptor</td><td>0.119</td><td>.</td></tr><tr><td>A0A3Q1M193</td><td>GP2</td><td>Glycoprotein 2</td><td>0.105</td><td>.</td></tr><tr><td>Q29S21</td><td>KRT7</td><td>Keratin, type II cytoskeletal 7</td><td>0.099</td><td>.</td></tr><tr><td>P17697</td><td>CLU</td><td>Clusterin</td><td>0.070</td><td>.</td></tr><tr><td>P11017</td><td>GNB2</td><td>Guanine nucleotide-binding protein G</td><td>0.065</td><td>.</td></tr><tr><td>P81265</td><td>PIGR</td><td>Polymeric immunoglobulin receptor</td><td>0.054</td><td>.</td></tr><tr><td>F1MKU3</td><td>BSPRY</td><td>B-box and SPRY domain containing</td><td>0.032</td><td>.</td></tr><tr><td>P27479</td><td>ALOX15</td><td>Polyunsaturated fatty acid lipoxygenase ALOX15</td><td>.</td><td>-0.378</td></tr><tr><td>P31039</td><td>SDHA</td><td>Succinate dehydrogenase</td><td>.</td><td>-0.345</td></tr><tr><td>F1N647</td><td>FASN</td><td>Fatty acid synthase</td><td>.</td><td>-0.224</td></tr><tr><td>Q28024</td><td>GNG12</td><td>Guanine nucleotide-binding protein G</td><td>.</td><td>-0.214</td></tr><tr><td>A7YY49</td><td>SURF4</td><td>Surfeit locus protein 4</td><td>.</td><td>-0.158</td></tr><tr><td>A2VDV2</td><td>STK38</td><td>Serine/threonine-protein kinase 38</td><td>.</td><td>-0.139</td></tr><tr><td>Q08E22</td><td>HID1</td><td>Chromosome 17 open reading frame 28 ortholog</td><td>.</td><td>-0.120</td></tr><tr><td>Q4GZT4</td><td>ABCG2</td><td>Broad substrate specificity ATP-binding cassette transporter ABCG2</td><td>.</td><td>-0.117</td></tr><tr><td>E1BPK6</td><td>MYO6</td><td>Unconventional myosin-VI</td><td>.</td><td>-0.111</td></tr><tr><td>P23004</td><td>UQCRC2</td><td>Cytochrome b-c1 complex subunit 2, mitochondrial</td><td>.</td><td>-0.076</td></tr><tr><td>A3KMV5</td><td>UBA1</td><td>Ubiquitin-like modifier-activating enzyme 1</td><td>.</td><td>-0.048</td></tr><tr><td>A3KN04</td><td>RPN1</td><td>Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1</td><td>.</td><td>-0.036</td></tr><tr><td>A0A3Q1MSN7</td><td>COASY</td><td>Coenzyme A synthase</td><td>.</td><td>-0.033</td></tr><tr><td>A0A3Q1LTV4</td><td>RAB3GAP2</td><td>RAB3 GTPase activating non-catalytic protein subunit 2</td><td>.</td><td>-0.030</td></tr><tr><td>A0A3Q1MFP2</td><td>RAB3GAP1</td><td>Rab3 GTPase-activating protein catalytic subunit</td><td>.</td><td>-0.023</td></tr></tbody></table>
<table><caption>Table 4: List of 30 proteins from component 1 of sparse multi-level multivariate analysis (sPLS – LPL activity) contributing to LL or HL group</caption><thead><tr><th rowspan="2">Accession</th><th rowspan="2">Gene name</th><th rowspan="2">Protein name</th><th colspan="2">Importance of contribution to comp1</th></tr><tr><th>HL</th><th>LL</th></tr></thead><tbody><tr><td>A0A3Q1M1</td><td>GP2</td><td>Glycoprotein 2</td><td>0.442</td><td></td></tr><tr><td>F1MKU3</td><td>BSPRY</td><td>B-box and SPRY domain containing</td><td>0.305</td><td></td></tr><tr><td>P06394</td><td>KRT10</td><td>Keratin, type I cytoskeletal 10</td><td>0.244</td><td></td></tr><tr><td>P20072</td><td>ANXA7</td><td>Annexin A7</td><td>0.208</td><td></td></tr><tr><td>P12624</td><td>MARCKS</td><td>Myristoylated alanine-rich C-kinase substrate</td><td>0.191</td><td></td></tr><tr><td>A6QNW7</td><td>CD5L</td><td>CD5 molecule like</td><td>0.164</td><td></td></tr><tr><td>E1B749</td><td>SLC5A9</td><td>Solute carrier family 5 member 9</td><td>0.147</td><td></td></tr><tr><td>O18875</td><td>SLC6A8</td><td>Sodium- and chloride-dependent creatine transporter 1</td><td>0.126</td><td></td></tr><tr><td>A0A3Q1M3</td><td>Uncharacterized protein</td><td>Immunoglobulin heavy constant mu</td><td>0.106</td><td></td></tr><tr><td>Q9XSG3</td><td>IDH1</td><td>Isocitrate dehydrogenase</td><td>0.104</td><td></td></tr><tr><td>Q29S21</td><td>KRT7</td><td>Keratin, type II cytoskeletal 7</td><td>0.079</td><td></td></tr><tr><td>E1BEH7</td><td>TC2N</td><td>Tandem C2 domains, nuclear</td><td>0.079</td><td></td></tr><tr><td>A0A3Q1LQ</td><td>CNTFR</td><td>Ciliary neurotrophic factor receptor</td><td>0.063</td><td></td></tr><tr><td>Y1</td><td></td><td>Alkaline phosphatase, tissue-nonspecific isozyme</td><td>0.056</td><td></td></tr><tr><td>P09487</td><td>ALPL</td><td>Endophilin-B1</td><td>0.046</td><td></td></tr><tr><td>Q32LM0</td><td>SH3GLB1</td><td>Erlin-2</td><td>0.036</td><td></td></tr><tr><td>Q1RMU4</td><td>ERLIN2</td><td>Alpha-soluble NSF attachment protein</td><td>0.015</td><td></td></tr><tr><td>P81125</td><td>NAPA</td><td>Chromosome 17 open reading frame 28 ortholog</td><td></td><td>-0.344</td></tr><tr><td>Q08E22</td><td>HID1</td><td>Squalene monooxygenase</td><td></td><td>-0.327</td></tr><tr><td>A5D9A8</td><td>SQLE</td><td>Cullin 9</td><td></td><td>-0.275</td></tr><tr><td>E1BM39</td><td>CUL9</td><td>Vesicle amine transport 1</td><td></td><td>-0.271</td></tr><tr><td>F1MUP9</td><td>VAT1</td><td>Prohibitin-2</td><td></td><td>-0.215</td></tr><tr><td>Q2HJ97</td><td>PHB2</td><td>Acyl-CoA synthetase long chain family member 3</td><td></td><td>-0.136</td></tr><tr><td>F1MEX9</td><td>ACSL3</td><td>NDRG family member 4</td><td></td><td>-0.100</td></tr><tr><td>A0A3Q1LV</td><td>NDRG4</td><td>ATPase 13A3</td><td></td><td>-0.083</td></tr><tr><td>G9</td><td>ATP13A3</td><td>Fatty acid synthase</td><td></td><td>-0.081</td></tr><tr><td>A0A3Q1LM</td><td>ANKRD13A</td><td>Ankyrin repeat domain 13A</td><td></td><td>-0.032</td></tr><tr><td>J5</td><td>AP2B1</td><td>AP-2 complex subunit beta</td><td></td><td>-0.020</td></tr><tr><td>P63009</td><td>AP2B1</td><td>CKLF-like MARVEL transmembrane domain-containing protein 8</td><td></td><td>-0.018</td></tr><tr><td>Q1RMP9</td><td>CMTM8</td><td>Surfeit locus protein 4</td><td></td><td>-0.010</td></tr><tr><td>A7YY49</td><td>SURF4</td><td>Surfeit locus protein 4</td><td></td><td>-0.010</td></tr></tbody></table>
<figure><img src="image_5.png" /><figcaption>Figure 1: Plot regression between lipolysis (mEq/100g of fat) and LPL activity in milk (nmol/mn/ml). Blue dots are from LL group and red dots are from HL group.</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>Figure 2: Volcano plot displays log fold changes on the x-axis versus a measure of statistical significance (Adjusted P-value) on the y-axis from the parametric univariate differential analysis (Diff-A). Gene Name of proteins with a higher abundance in HL than LL group are in blue. Gene Name of proteins with a lower abundance in HL than in LL group are in orange.</figcaption></figure>
<figure><img src="image_7.png" /><figcaption>Figure 3: Venn diagram comparing proteins lists addressing HL group from sPLS-lipolysis (n=15), sPLS-LPL-activity (n=17) and differential analysis (n=7).</figcaption></figure>
<figure><img src="image_8.png" /><figcaption>Figure 4: Venn diagram comparing proteins lists addressing LL group from sPLS-lipolysis (n=15), sPLS-LPL-activity (n=13) and differential analysis (n=1).</figcaption></figure>
<table><caption>Supplementary Table S1: Dry matter, protein and energy intakes, energy balance and efficiency of protein digestible in intestine for LL and HL groups of cows</caption><thead><tr><th></th><th>LL</th><th>HL</th><th>SEM</th><th>p-val<br>lipolysis</th><th>Signifi<br>cance of<br>lipolysi<br>s</th><th>Signific<br>ance of<br>period</th></tr></thead><tbody><tr><td>DMI (kg/d)</td><td>21,1</td><td>15,8</td><td>0,8</td><td>0,000</td><td>***</td><td>NS</td></tr><tr><td>PDI* (g/d)</td><td>1761,6</td><td>1306,1</td><td>74,9</td><td>0,000</td><td>***</td><td>NS</td></tr><tr><td>NEL requirements (MJ/d)</td><td>19,69</td><td>17,56</td><td>0,65</td><td>0,016</td><td>*</td><td>NS</td></tr><tr><td>PDI efficiency**</td><td>0,83</td><td>0,84</td><td>0,01</td><td>0,023</td><td>*</td><td>**</td></tr><tr><td>NEL balance (MJ/kg DM)</td><td>-5,7</td><td>-21,9</td><td>2,8</td><td>0,003</td><td>**</td><td>NS</td></tr></tbody></table>

<footnote>*PDI = protein digestible in the intestine (INRA, 2018)</footnote>

<footnote>**PDI efficiency = (67,5-0,52 x (PDI-100) + 0,014 x (MilkProteins-1000))/100 (INRA, 2018)</footnote>
<table><caption>sPLS_Lipolysis_Enrichment_GO_GP_of_15prot_contributing_to_HL_group</caption><thead><tr><th>GO_BP</th><th>Function</th><th>Gene Name</th><th>Term frequency v Term frequency P-value (fdr)</th><th>Query with no gene names</th></tr></thead><tbody><tr><td>GO:0010873</td><td>positive regulation of cholesterol esterification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0034433</td><td>steroid esterification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0034372</td><td>very-low-density lipoprotein particle remodeling</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0034370</td><td>triglyceride-rich lipoprotein particle remodeling</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0034434</td><td>sterol esterification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0010872</td><td>regulation of cholesterol esterification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0034435</td><td>cholesterol esterification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0043691</td><td>reverse cholesterol transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>6,0736E-06</td></tr><tr><td>GO:0033700</td><td>phospholipid efflux</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>7,00849E-06</td></tr><tr><td>GO:0045940</td><td>positive regulation of steroid metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>15.79 3/19</td></tr><tr><td>GO:0065005</td><td>protein-lipid complex assembly</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.13232E-05</td></tr><tr><td>GO:0034369</td><td>plasma lipoprotein particle remodeling</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.27971E-05</td></tr><tr><td>GO:0034368</td><td>protein-lipid complex remodeling</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.36038E-05</td></tr><tr><td>GO:1903494</td><td>response to dehydroepiandrosterone</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.69778E-05</td></tr><tr><td>GO:1903496</td><td>response to 11-deoxycorticosterone</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.69778E-05</td></tr><tr><td>GO:0034367</td><td>protein-containing complex remodeling</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.77948E-05</td></tr><tr><td>GO:0071827</td><td>plasma lipoprotein particle organization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>5.92498E-05</td></tr><tr><td>GO:1902995</td><td>positive regulation of phospholipid efflux</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>66.67 2/3</td></tr><tr><td>GO:1902994</td><td>regulation of phospholipid efflux</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>66.67 2/3</td></tr><tr><td>GO:0071825</td><td>protein-lipid complex subunit organization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>8.82 3/34</td></tr><tr><td>GO:0010033</td><td>response to organic substance</td><td>APOA1 APOA4 APOE</td><td>69.23 9/13</td><td>0.419 2222</td></tr><tr><td>GO:0090207</td><td>regulation of triglyceride metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>9.59250E-05</td></tr><tr><td>GO:0032374</td><td>regulation of cholesterol transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>9.59250E-05</td></tr><tr><td>GO:0033344</td><td>cholesterol efflux</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000115493</td></tr><tr><td>GO:0032371</td><td>regulation of sterol transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000115493</td></tr><tr><td>GO:0120009</td><td>intermembrane lipid transfer</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000115493</td></tr><tr><td>GO:0097006</td><td>regulation of plasma lipoprotein particle levels</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000139447</td></tr><tr><td>GO:0032489</td><td>regulation of Cdc42 protein signal transduction</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>33.33 2/6</td></tr><tr><td>GO:0046889</td><td>positive regulation of lipid biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>5.173 5/8</td></tr><tr><td>GO:0051385</td><td>response to mineralocorticoid</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>28.57 2/7</td></tr><tr><td>GO:0042632</td><td>cholesterol homeostasis</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>4.623 6/5</td></tr><tr><td>GO:0055092</td><td>stero homeostasis</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>4.55 3/66</td></tr><tr><td>GO:0034380</td><td>high-density lipoprotein particle assembly</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>25.00 2/8</td></tr><tr><td>GO:0051129</td><td>negative regulation of cellular component organization</td><td>APOA1 APOA4 APOE</td><td>43.6 4/13</td><td>0.99 5/507</td></tr><tr><td>GO:0019218</td><td>regulation of steroid metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>4.23 3/11</td></tr><tr><td>GO:0051006</td><td>positive regulation of lipoprotein lipase activity</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>22.22 2/9</td></tr><tr><td>GO:0016125</td><td>positive regulation of phospholipid transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>22.22 2/9</td></tr><tr><td>GO:0010898</td><td>positive regulation of triglyceride catabolic process</td><td>APOA1 APOA4 APOE</td><td>20.00 2/10</td><td>0.00042225</td></tr><tr><td>GO:0061365</td><td>positive regulation of triglyceride lipase activity</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.00042225</td></tr><tr><td>GO:2001138</td><td>regulation of phospholipid transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.00042225</td></tr><tr><td>GO:0030301</td><td>cholesterol transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>3.80 3/79</td></tr><tr><td>GO:0042221</td><td>response to chemical</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.25 10/4056</td></tr><tr><td>GO:1905907</td><td>negative regulation of amyloid fibril formation</td><td>APOA1 APOA4 APOE</td><td>69.72 10/13</td><td>0.000335406</td></tr><tr><td>GO:0006641</td><td>triglyceride metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.000335406</td></tr><tr><td>GO:0032368</td><td>regulation of lipid transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>20.00 2/10</td></tr><tr><td>GO:0032488</td><td>Cdc42 protein signal transduction</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>3.613 3/8</td></tr><tr><td>GO:0034375</td><td>high-density lipoprotein particle remodeling</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>35.78 3/84</td></tr><tr><td>GO:0032570</td><td>response to prostegesterone</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>18.18 2/11</td></tr><tr><td>GO:1905906</td><td>regulation of amyloid fibril formation</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>16.67 2/12</td></tr><tr><td>GO:0098869</td><td>cellular oxidant detoxification</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>16.67 2/12</td></tr><tr><td>GO:0015918</td><td>sterol transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>16.67 2/12</td></tr><tr><td>GO:0010896</td><td>regulation of triglyceride catabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>3.23 3/9</td></tr><tr><td>GO:0051004</td><td>regulation of lipoprotein lipase activity</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>3.19 3/94</td></tr><tr><td>GO:0008203</td><td>cholesterol metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.000582178</td></tr><tr><td>GO:0015914</td><td>phospholipid transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>15.38 2/13</td></tr><tr><td>GO:206252</td><td>secondary alcohol metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000582178</td></tr><tr><td>GO:0016125</td><td>sterol metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.000609081</td></tr><tr><td>GO:1902903</td><td>regulation of supramolecular fiber organization</td><td>APOA1 APOA4 APOE</td><td>10.00 2/10</td><td>0.00063511</td></tr><tr><td>GO:0045834</td><td>positive regulation of lipid metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>1.274 3/15</td></tr><tr><td>GO:1990748</td><td>cellular detoxification</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.88 3/104</td></tr><tr><td>GO:1990592</td><td>regulation of lipid localization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.86 3/105</td></tr><tr><td>GO:0097237</td><td>cellular response to toxic substance</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.00066794</td></tr><tr><td>GO:0034377</td><td>plasma lipoprotein particle assembly</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.000740408</td></tr><tr><td>GO:0006869</td><td>lipid transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>2.73 3/110</td></tr><tr><td>GO:0006639</td><td>acylglycerol metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.73 3/110</td></tr><tr><td>GO:0006638</td><td>neutral lipid metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>12.50 2/16</td></tr><tr><td>GO:1990000</td><td>amyloid fibril formation</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.00067008</td></tr><tr><td>GO:0031331</td><td>positive regulation of cellular catabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>1.26 3/139</td></tr><tr><td>GO:0010875</td><td>regulation of cholesterol efflux</td><td>APOA1 APOA4 APOE</td><td>10.00 2/10</td><td>0.000114562</td></tr><tr><td>GO:0098754</td><td>detoxification</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>11.76 2/17</td></tr><tr><td>GO:0055088</td><td>lipid homeostasis</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>11.76 2/17</td></tr><tr><td>GO:0046890</td><td>regulation of lipid biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.54 3/118</td></tr><tr><td>GO:0045723</td><td>positive regulation of fatty acid biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.50 3/120</td></tr><tr><td>GO:0010876</td><td>lipid localization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.42 3/124</td></tr><tr><td>GO:0006014</td><td>response to growth hormone</td><td>APOA1 APOA4 APOE</td><td>10.00 2/10</td><td>0.000911385</td></tr><tr><td>GO:0042157</td><td>lipoprotein metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.01020122</td></tr><tr><td>GO:0090208</td><td>regulation of triglyceride metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.01020122</td></tr><tr><td>GO:0016125</td><td>male sterol response</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.01020122</td></tr><tr><td>GO:0055090</td><td>triglyceride homeostasis</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.01145662</td></tr><tr><td>GO:0070328</td><td>triglyceride homeostasis</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.01145662</td></tr><tr><td>GO:1902904</td><td>negative regulation of supramolecular fiber organization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>1.04 4/400</td></tr><tr><td>GO:0009896</td><td>positive regulation of catabolic process</td><td>APOA1 APOA4 APOE</td><td>23.07 7/43</td><td>0.001208571</td></tr><tr><td>GO:0015748</td><td>organophosphate ester transport</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.10 3/143</td></tr><tr><td>GO:0050996</td><td>positive regulation of lipid catabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>8.70 2/23</td></tr><tr><td>GO:0050821</td><td>protein stabilization</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>2.04 3/147</td></tr><tr><td>GO:0002376</td><td>immune system process</td><td>APOA1 APOA4 APOE</td><td>CLI 35.85 7/13</td><td>0.347 2045</td></tr><tr><td>GO:0009636</td><td>response to toxic substance</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>1.99 3/151</td></tr><tr><td>GO:0002251</td><td>organ or tissue specific immune response</td><td>APOA1 APOA4 APOE</td><td>8.00 2/25</td><td>0.00135265</td></tr><tr><td>GO:0010874</td><td>regulation of cholesterol efflux</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.00135265</td></tr><tr><td>GO:0032376</td><td>positive regulation of cholesterol transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>8.00 2/25</td></tr><tr><td>GO:0032373</td><td>positive regulation of sterol transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.00135265</td></tr><tr><td>GO:0019433</td><td>triglyceride catabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>7.69 2/26</td></tr><tr><td>GO:0045923</td><td>positive regulation of fatty acid metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.001432643</td></tr><tr><td>GO:0033993</td><td>response to lipid</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>7.69 2/26</td></tr><tr><td>GO:0032355</td><td>response to estradiol</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.001432643</td></tr><tr><td>GO:0030258</td><td>lipid modification</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>7.41 2/27</td></tr><tr><td>GO:0046461</td><td>neutral lipid catabolic process</td><td>APOA1 APOA4 APOE</td><td>30.77 4/13</td><td>6.67 2/30</td></tr><tr><td>GO:1902653</td><td>secondary alcohol biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.86 4/664</td></tr><tr><td>GO:0042304</td><td>regulation of fatty acid biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>6.25 2/32</td></tr><tr><td>GO:0006695</td><td>cholesterol biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>1.60 3/187</td></tr><tr><td>GO:0046464</td><td>acylglycerol catabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.002308728</td></tr><tr><td>GO:0015850</td><td>organic hydroxy compound transport</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.002493052</td></tr><tr><td>GO:0016126</td><td>sterol biosynthetic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.002493052</td></tr><tr><td>GO:0070887</td><td>cellular response to chemical stimulus</td><td>APOA1 APOA4 APOE</td><td>53.85 7/13</td><td>0.29 7/2376</td></tr><tr><td>GO:0031960</td><td>response to corticosteroid</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>4.88 2/41</td></tr><tr><td>GO:0043113</td><td>receptor clustering</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>4.76 2/42</td></tr><tr><td>GO:0050727</td><td>regulation of inflammatory response</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>0.003251371</td></tr><tr><td>GO:0060193</td><td>positive regulation of lipase activity</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>0.003333248</td></tr><tr><td>GO:0008020</td><td>steroid metabolic process</td><td>APOA1 APOA4 APOE</td><td>13.13 2/229</td><td>0.003686906</td></tr><tr><td>GO:0031647</td><td>regulation of protein stability</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>1.30 3/231</td></tr><tr><td>GO:0062012</td><td>regulation of small molecule metabolic process</td><td>APOA1 APOA4 APOE</td><td>23.08 3/13</td><td>1.273 2/326</td></tr><tr><td>GO:0046470</td><td>phosphatidylcholine metabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>4.08 2/49</td></tr><tr><td>GO:0050994</td><td>regulation of lipid catabolic process</td><td>APOA1 APOA4 APOE</td><td>15.38 2/13</td><td>4.08 2/49</td></tr></tbody></table>
<table><tr><td>GO:0031324</td><td>negative regulation of cellular metabolic process</td></tr><tr><td>GO:0044271</td><td>cellular nitrogen compound biosynthetic process</td></tr><tr><td>GO:0071704</td><td>organic substance metabolic process</td></tr><tr><td>GO:0006807</td><td>nitrogen compound metabolic process</td></tr><tr><td>GO:0044238</td><td>primary metabolic process</td></tr><tr><td>GO:0008152</td><td>metabolic process</td></tr><tr><td>GO:0006996</td><td>organelle organization</td></tr><tr><td>GO:0016070</td><td>RNA metabolic process</td></tr><tr><td>GO:0009987</td><td>cellular process</td></tr><tr><td>GO:0090304</td><td>nucleic acid metabolic process</td></tr><tr><td>GO:0044237</td><td>cellular metabolic process</td></tr><tr><td>GO:0006139</td><td>nucleobase-containing compound metabolic process</td></tr><tr><td>GO:0046483</td><td>heterocycle metabolic process</td></tr><tr><td>GO:0006725</td><td>cellular aromatic compound metabolic process</td></tr><tr><td>GO:0034641</td><td>cellular nitrogen compound metabolic process</td></tr><tr><td>GO:0008150</td><td>biological_process</td></tr></table>

<table><tr><td>Any process that stops, prevents, or reduces the frequency, rate or APOE</td><td>7.69 1/13</td><td>0.05 1/2035</td><td>0.761153639</td></tr><tr><td>The chemical reactions and pathways resulting in the formation of APOE CLU</td><td>15.38 2/13</td><td>0.05 2/4213</td><td>0.801554622</td></tr><tr><td>The chemical reactions and pathways involving an organic substan APOA1 APOA4 APOE BSI 53.85 7/13</td><td>0.06 7/12360</td><td>0.813612225</td><td></td></tr><tr><td>The chemical reactions and pathways involving organic or inorganic APOA1 APOA4 APOE BSI 46.15 6/13</td><td>0.05 6/10926</td><td>0.817432796</td><td></td></tr><tr><td>The chemical reactions and pathways involving those compounds \ APOA1 APOA4 APOE BSI 46.15 6/13</td><td>0.05 6/11429</td><td>0.863735743</td><td></td></tr><tr><td>The chemical reactions and pathways, including anabolism and cat APOA1 APOA4 APOE BSI 53.85 7/13</td><td>0.05 7/12915</td><td>0.865498758</td><td></td></tr><tr><td>A process that is carried out at the cellular level which results in the APOA1</td><td>7.69 1/13</td><td>0.03 1/3330</td><td>0.9128581</td></tr><tr><td>The cellular chemical reactions and pathways involving RNA, ribon APOE CLU</td><td>15.38 2/13</td><td>0.03 2/5843</td><td>0.934248931</td></tr><tr><td>Any process that is carried out at the cellular level, but not necessa APOA1 APOA4 APOE BSI 84.62 11/13</td><td>0.06 11/18706</td><td>0.949011927</td><td></td></tr><tr><td>Any cellular metabolic process involving nucleic acids. APOE CLU</td><td>15.38 2/13</td><td>0.03 2/6311</td><td>0.953583437</td></tr><tr><td>The chemical reactions and pathways by which individual cells tran APOA1 APOA4 APOE BSI 38.46 5/13</td><td>0.04 5/11581</td><td>0.95708073</td><td></td></tr><tr><td>Any cellular metabolic process involving nucleobases, nucleosides, APOE CLU</td><td>15.38 2/13</td><td>0.03 2/6721</td><td>0.965715164</td></tr><tr><td>The chemical reactions and pathways involving heterocyclic compc APOE CLU</td><td>15.38 2/13</td><td>0.03 2/6828</td><td>0.967847786</td></tr><tr><td>The chemical reactions and pathways involving aromatic compoun APOE CLU</td><td>15.38 2/13</td><td>0.03 2/6891</td><td>0.968619603</td></tr><tr><td>The chemical reactions and pathways involving various organic and APOE CLU</td><td>15.38 2/13</td><td>0.03 2/7596</td><td>0.982311673</td></tr><tr><td>A biological process represents a specific objective that the organis APOA1 APOA4 APOE BSI 100.00 13/13</td><td>0.06 13/20110</td><td>1</td><td></td></tr></table>
sPLS_LPLactivity_Enrichment_GO献_of_17prot_contributing_to_HL_group

<table>
  <thead>
    <tr>
      <th>GO献</th>
      <th>Name</th>
      <th>Function</th>
      <th>Gene Name</th>
      <th>Term freque</th>
      <th>Term frequ</th>
      <th>P-value (fdr)</th>
    </tr>
  </thead>
  <tbody>
    <tr>
      <td>GO:0090206</td>
      <td>negative regulation of cholesterol metabolic process</td>
      <td>Any process that decreases the rate, frequency, or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0006102</td>
      <td>isocitrate metabolic process</td>
      <td>The chemical reactions and pathways involving isocitrate, 1IDH</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>33.33 1/3</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0006097</td>
      <td>glyoxylate cycle</td>
      <td>A modification of the TCA cycle occurring in some plants a 1IDH</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>50.00 1/2</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0006081</td>
      <td>cellular aldehyde metabolic process</td>
      <td>The chemical reactions and pathways involving aldehydes, ALPL IDH1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>3.85 2/52</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:1903778</td>
      <td>protein localization to vacuolar membrane</td>
      <td>A process in which a protein is transported to, or maintain SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>100.00 1/1</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:1903527</td>
      <td>positive regulation of membrane tubulation</td>
      <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0045541</td>
      <td>negative regulation of cholesterol biosynthetic process</td>
      <td>Any process that stops, prevents, or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0106119</td>
      <td>negative regulation of sterol biosynthetic process</td>
      <td>Any process that stops, prevents or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:1901616</td>
      <td>organic hydroxy compound metabolic process</td>
      <td>The chemical reactions and pathways involving organic hyd ALPL ERLIN2 IDH1</td>
      <td></td>
      <td>21.43 3/14</td>
      <td>0.75 3/398</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:1902652</td>
      <td>secondary alcohol metabolic process</td>
      <td>The chemical reactions and pathways involving secondary ERLIN2 IDH1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>1.98 2/101</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0003360</td>
      <td>brainstem development</td>
      <td>The progression of the brainstem from its formation to the CNTRL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0042822</td>
      <td>pyridoxal phosphate metabolic process</td>
      <td>The chemical reactions and pathways involving pyridoxal p ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0015881</td>
      <td>creatine transmembrane transport</td>
      <td>The directed movement of creatine across a membrane. SLC6A8</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>50.00 1/2</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0042816</td>
      <td>vitamin B6 metabolic process</td>
      <td>The chemical reactions and pathways involving any of the ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>25.00 1/4</td>
      <td>0,079087858</td>
    </tr>
    <tr>
      <td>GO:0046890</td>
      <td>regulation of lipid biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2 IDH1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>1.61 2/124</td>
      <td>0,08647439</td>
    </tr>
    <tr>
      <td>GO:0060696</td>
      <td>regulation of phospholipid catabolic process</td>
      <td>Any process that modulates the rate, frequency, or extent IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>20.00 1/5</td>
      <td>0,08647439</td>
    </tr>
    <tr>
      <td>GO:0046487</td>
      <td>glyoxylate metabolic process</td>
      <td>The chemical reactions and pathways involving glyoxylate, IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>14.29 1/7</td>
      <td>0,092179749</td>
    </tr>
    <tr>
      <td>GO:0070120</td>
      <td>ciliary neurotrophic factor-mediated signaling pathway</td>
      <td>A series of molecular signals initiated by the binding of a ci CNTRL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>14.29 1/7</td>
      <td>0,092179749</td>
    </tr>
    <tr>
      <td>GO:1903525</td>
      <td>regulation of membrane tubulation</td>
      <td>Any process that modulates the frequency, rate or extent &lt; SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>14.29 1/7</td>
      <td>0,092179749</td>
    </tr>
    <tr>
      <td>GO:0090148</td>
      <td>membrane fission</td>
      <td>A process that is carried out at the cellular level which res SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>14.29 1/7</td>
      <td>0,092179749</td>
    </tr>
    <tr>
      <td>GO:0048102</td>
      <td>autophagic cell death</td>
      <td>A form of programmed cell death that is accompanied by t SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>16.67 1/6</td>
      <td>0,092179749</td>
    </tr>
    <tr>
      <td>GO:0106118</td>
      <td>regulation of sterol biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>10.00 1/10</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0001967</td>
      <td>suckling behavior</td>
      <td>Specific behavior of a newborn or infant mammal that res CNTRL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>11.11 1/9</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:1902931</td>
      <td>negative regulation of alcohol biosynthetic process</td>
      <td>Any process that stops, prevents or reduces the frequency ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>9.09 1/11</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0006103</td>
      <td>2-oxoglutarate metabolic process</td>
      <td>The chemical reactions and pathways involving oxoglutaral IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>10.00 1/10</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0072350</td>
      <td>tricarboxylic acid metabolic process</td>
      <td>The chemical reactions and pathways involving dicarboxyli IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>9.09 1/11</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0071071</td>
      <td>regulation of phospholipid biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>8.33 1/12</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0006814</td>
      <td>sodium ion transport</td>
      <td>The directed movement of sodium ions (Na+) into, out of &lt; SLC5A9 SLC6A8</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>1.00 2/200</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0051764</td>
      <td>actin crosslink formation</td>
      <td>The process in which two or more actin filaments are conn MARCKS</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>9.09 1/11</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0045540</td>
      <td>regulation of cholesterol biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>10.00 1/10</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0045717</td>
      <td>negative regulation of fatty acid biosynthetic process</td>
      <td>Any process that stops, prevents, or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>8.33 1/12</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0051290</td>
      <td>protein heterotetramerization</td>
      <td>The formation of a protein heterotetramer, a macromolecule KRT10</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>10.00 1/10</td>
      <td>0,103534823</td>
    </tr>
    <tr>
      <td>GO:0071501</td>
      <td>cellular response to sterol depletion</td>
      <td>Any process that results in a change in state or activity of a ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>7.69 1/13</td>
      <td>0,105530823</td>
    </tr>
    <tr>
      <td>GO:0032933</td>
      <td>SREBP signaling pathway</td>
      <td>A series of molecular signals from the endoplasmic reticulit ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>7.69 1/13</td>
      <td>0,105530823</td>
    </tr>
    <tr>
      <td>GO:1903729</td>
      <td>regulation of plasma membrane organization</td>
      <td>Any process that modulates the frequency, rate or extent &lt; SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>7.14 1/14</td>
      <td>0,107300105</td>
    </tr>
    <tr>
      <td>GO:0006991</td>
      <td>response to sterol depletion</td>
      <td>Any process that results in a change in state or activity of a ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>7.14 1/14</td>
      <td>0,107300105</td>
    </tr>
    <tr>
      <td>GO:2000786</td>
      <td>positive regulation of autophagosome assembly</td>
      <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>6.67 1/15</td>
      <td>0,111821131</td>
    </tr>
    <tr>
      <td>GO:0033280</td>
      <td>response to vitamin D</td>
      <td>Any process that results in a change in state or activity of a ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>6.25 1/16</td>
      <td>0,116099533</td>
    </tr>
    <tr>
      <td>GO:0031667</td>
      <td>response to nutrient levels</td>
      <td>Any process that results in a change in state or activity of a ALPL SH3GLB1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.79 2/252</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0019216</td>
      <td>regulation of lipid metabolic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2 IDH1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.81 2/246</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0090181</td>
      <td>regulation of cholesterol metabolic process</td>
      <td>Any process that modulates the rate, frequency, or extent ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.00 1/20</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0045939</td>
      <td>negative regulation of steroid metabolic process</td>
      <td>Any process that stops, prevents, or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.00 1/20</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0097320</td>
      <td>plasma membrane tubulation</td>
      <td>A membrane tubulation process occurring in a plasma mer SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.26 1/19</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0010894</td>
      <td>negative regulation of steroid biosynthetic process</td>
      <td>Any process that decreases the frequency, rate or extent o ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.00 1/20</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0044090</td>
      <td>positive regulation of vacuole organization</td>
      <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.56 1/18</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0051291</td>
      <td>protein heterooligomerization</td>
      <td>The process of creating protein oligomers, compounds cor KRT10</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>5.56 1/18</td>
      <td>0,119730648</td>
    </tr>
    <tr>
      <td>GO:0006066</td>
      <td>alcohol metabolic process</td>
      <td>The chemical reactions and pathways involving alcohols, a ERLIN2 IDH1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.75 2/266</td>
      <td>0,120950404</td>
    </tr>
    <tr>
      <td>GO:0009991</td>
      <td>response to extracellular stimulus</td>
      <td>Any process that results in a change in state or activity of a ALPL SH3GLB1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.73 2/273</td>
      <td>0,12108921</td>
    </tr>
    <tr>
      <td>GO:0045922</td>
      <td>negative regulation of fatty acid metabolic process</td>
      <td>Any process that stops, prevents, or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.55 1/22</td>
      <td>0,12108921</td>
    </tr>
    <tr>
      <td>GO:0032801</td>
      <td>receptor catabolic process</td>
      <td>The chemical reactions and pathways resulting in the break SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.55 1/22</td>
      <td>0,12108921</td>
    </tr>
    <tr>
      <td>GO:0033273</td>
      <td>response to vitamin</td>
      <td>Any process that results in a change in state or activity of a ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.85 1/26</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0001958</td>
      <td>endochondral ossification</td>
      <td>Replacement ossification wherein bone tissue replaces car ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.85 1/26</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0072337</td>
      <td>modified amino acid transport</td>
      <td>The directed movement of modified amino acids into, out SLC6A8</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.35 1/23</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0006767</td>
      <td>water-soluble vitamin metabolic process</td>
      <td>The chemical reactions and pathways involving any of a di ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.85 1/26</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0036075</td>
      <td>replacement ossification</td>
      <td>Ossification that requires the replacement of a preexisting ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.85 1/26</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0046677</td>
      <td>response to antibiotic</td>
      <td>Any process that results in a change in state or activity of a ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.35 1/23</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0018149</td>
      <td>peptide cross-linking</td>
      <td>The formation of a covalent cross-link between or within p KRT10</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.00 1/25</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:0072524</td>
      <td>pyridine-containing compound metabolic process</td>
      <td>The chemical reactions and pathways involving a pyridine- ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.85 1/26</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:1903725</td>
      <td>regulation of phospholipid metabolic process</td>
      <td>Any process that modulates the frequency, rate or extent IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.00 1/25</td>
      <td>0,121119324</td>
    </tr>
    <tr>
      <td>GO:1902930</td>
      <td>regulation of steroid biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>4.00 1/25</td>
      <td>0,121614649</td>
    </tr>
    <tr>
      <td>GO:0006739</td>
      <td>NADP metabolic process</td>
      <td>The chemical reactions and pathways involving nicotinamid IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.70 1/27</td>
      <td>0,121614649</td>
    </tr>
    <tr>
      <td>GO:0006099</td>
      <td>tricarboxylic acid cycle</td>
      <td>A nearly universal metabolic pathway in which the acetyl g state</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>3.57 1/28</td>
      <td>0,124044689</td>
    </tr>
    <tr>
      <td>GO:0007584</td>
      <td>response to nutrient</td>
      <td>Any process that results in a change in state or activity of a ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.94 1/34</td>
      <td>0,147948184</td>
    </tr>
    <tr>
      <td>GO:0042304</td>
      <td>regulation of fatty acid biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.78 1/36</td>
      <td>0,149434108</td>
    </tr>
    <tr>
      <td>GO:0006695</td>
      <td>cholesterol biosynthetic process</td>
      <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.78 1/36</td>
      <td>0,149434108</td>
    </tr>
    <tr>
      <td>GO:1902653</td>
      <td>secondary alcohol biosynthetic process</td>
      <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.78 1/36</td>
      <td>0,149434108</td>
    </tr>
    <tr>
      <td>GO:0009395</td>
      <td>phospholipid catabolic process</td>
      <td>The chemical reactions and pathways resulting in the break IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.44 1/41</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:2000785</td>
      <td>regulation of autophagosome assembly</td>
      <td>Any process that modulates the frequency, rate or extent &lt; SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.50 1/40</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0042149</td>
      <td>cellular response to glucose starvation</td>
      <td>Any process that results in a change in state or activity of a SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.50 1/40</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0061919</td>
      <td>process utilizing autophagic mechanism</td>
      <td>A cellular process involving delivery of a portion of the cyti ANXA7 SH3GLB1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.52 2/382</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0051055</td>
      <td>negative regulation of lipid biosynthetic process</td>
      <td>Any process that stops, prevents, or reduces the frequency, ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.50 1/40</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0006914</td>
      <td>autophagy</td>
      <td>The cellular catabolic process in which cells digest parts of ANXA7 SH3GLB1</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.52 2/382</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0016126</td>
      <td>sterol biosynthetic process</td>
      <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.56 1/39</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0006984</td>
      <td>ER-nucleus signaling pathway</td>
      <td>Any series of molecular signals that conveys information fr ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.63 1/38</td>
      <td>0,151545566</td>
    </tr>
    <tr>
      <td>GO:0034198</td>
      <td>cellular response to amino acid starvation</td>
      <td>Any process that results in a change in state or activity of a SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.38 1/42</td>
      <td>0,153122546</td>
    </tr>
    <tr>
      <td>GO:1990928</td>
      <td>response to amino acid starvation</td>
      <td>Any process that results in a change in state or activity of a SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.33 1/43</td>
      <td>0,154655727</td>
    </tr>
    <tr>
      <td>GO:0044088</td>
      <td>regulation of vacuole organization</td>
      <td>Any process that modulates the frequency, rate or extent &lt; SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.27 1/44</td>
      <td>0,156146816</td>
    </tr>
    <tr>
      <td>GO:0044248</td>
      <td>cellular catabolic process</td>
      <td>The chemical reactions and pathways resulting in the bre: ANXA7 ERLIN2 IDH</td>
      <td>28.57 4/14</td>
      <td>0.22 4/181</td>
      <td>0,161534441</td>
    </tr>
    <tr>
      <td>GO:0050994</td>
      <td>regulation of lipid catabolic process</td>
      <td>Any process that modulates the frequency, rate, or extent IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.04 1/49</td>
      <td>0,169215648</td>
    </tr>
    <tr>
      <td>GO:0050810</td>
      <td>regulation of steroid biosynthetic process</td>
      <td>Any process that modulates the frequency, rate or extent &lt; ERLIN2</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>2.00 1/50</td>
      <td>0,170455749</td>
    </tr>
    <tr>
      <td>GO:0060350</td>
      <td>endochondral bone morphogenesis</td>
      <td>The process in which bones are generated and organized a ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.96 1/51</td>
      <td>0,171663082</td>
    </tr>
    <tr>
      <td>GO:0006766</td>
      <td>vitamin metabolic process</td>
      <td>The chemical reactions and pathways involving vitamins. V ALPL</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.89 1/53</td>
      <td>0,176105947</td>
    </tr>
    <tr>
      <td>GO:0006749</td>
      <td>glutathione metabolic process</td>
      <td>The chemical reactions and pathways involving glutathion IDH1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.85 1/54</td>
      <td>0,177209833</td>
    </tr>
    <tr>
      <td>GO:0016239</td>
      <td>positive regulation of macroautophagy</td>
      <td>Any process, such as recognition of nutrient depletion, tha SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.79 1/56</td>
      <td>0,181468483</td>
    </tr>
    <tr>
      <td>GO:0072665</td>
      <td>protein localization to vacuole</td>
      <td>A process in which a protein is transported to, or maintain SH3GLB1</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.67 1/60</td>
      <td>0,184241808</td>
    </tr>
    <tr>
      <td>GO:0031638</td>
      <td>zymogen activation</td>
      <td>The proteolytic processing of an inactive enzyme to an acti CD5L</td>
      <td></td>
      <td>7.14 1/14</td>
      <td>1.69 1/59</td>
      <td>0,184241808</td>
    </tr>
    <tr>
      <td>GO:0030855</td>
      <td>epithelial cell differentiation</td>
      <td>The process in which a relatively unspecialized cell acquire ANXA7 KRT10</td>
      <td></td>
      <td>14.29 2/14</td>
      <td>0.43 2/470</td>
      <td>0,184241808</td>
    </tr>
  </tbody>
</table>
<table>
  <tr>
    <td>GO:0032787</td>
    <td>monocarboxylic acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0043648</td>
    <td>dicarboxylic acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0120162</td>
    <td>positive regulation of cold-induced thermogenesis</td>
  </tr>
  <tr>
    <td>GO:0007631</td>
    <td>feeding behavior</td>
  </tr>
  <tr>
    <td>GO:0062014</td>
    <td>negative regulation of small molecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0051262</td>
    <td>protein tetramerization</td>
  </tr>
  <tr>
    <td>GO:1902117</td>
    <td>positive regulation of organelle assembly</td>
  </tr>
  <tr>
    <td>GO:0019217</td>
    <td>regulation of fatty acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0019218</td>
    <td>regulation of steroid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0045833</td>
    <td>negative regulation of lipid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0008616</td>
    <td>lipid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0009056</td>
    <td>catabolic process</td>
  </tr>
  <tr>
    <td>GO:0032465</td>
    <td>regulation of cytokinesis</td>
  </tr>
  <tr>
    <td>GO:1904659</td>
    <td>glucose transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0060349</td>
    <td>bone morphogenesis</td>
  </tr>
  <tr>
    <td>GO:1990823</td>
    <td>response to leukemia inhibitory factor</td>
  </tr>
  <tr>
    <td>GO:0008645</td>
    <td>hexose transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0030433</td>
    <td>ubiquitin-dependent ERAD pathway</td>
  </tr>
  <tr>
    <td>GO:0015718</td>
    <td>monocarboxylic acid transport</td>
  </tr>
  <tr>
    <td>GO:1990830</td>
    <td>cellular response to leukemia inhibitory factor</td>
  </tr>
  <tr>
    <td>GO:0015749</td>
    <td>monosaccharide transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0034219</td>
    <td>carbohydrate transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0010033</td>
    <td>response to organic substance</td>
  </tr>
  <tr>
    <td>GO:0016241</td>
    <td>regulation of macroautophagy</td>
  </tr>
  <tr>
    <td>GO:0008203</td>
    <td>cholesterol metabolic process</td>
  </tr>
  <tr>
    <td>GO:0030216</td>
    <td>keratinocyte differentiation</td>
  </tr>
  <tr>
    <td>GO:0030282</td>
    <td>bone mineralization</td>
  </tr>
  <tr>
    <td>GO:0010565</td>
    <td>regulation of cellular ketone metabolic process</td>
  </tr>
  <tr>
    <td>GO:0031329</td>
    <td>regulation of cellular catabolic process</td>
  </tr>
  <tr>
    <td>GO:0106106</td>
    <td>cold-induced thermogenesis</td>
  </tr>
  <tr>
    <td>GO:0000045</td>
    <td>autophagosome assembly</td>
  </tr>
  <tr>
    <td>GO:1990266</td>
    <td>neutrophil migration</td>
  </tr>
  <tr>
    <td>GO:1905037</td>
    <td>autophagosome organization</td>
  </tr>
  <tr>
    <td>GO:0120161</td>
    <td>regulation of cold-induced thermogenesis</td>
  </tr>
  <tr>
    <td>GO:1990845</td>
    <td>adaptive thermogenesis</td>
  </tr>
  <tr>
    <td>GO:0016125</td>
    <td>sterol metabolic process</td>
  </tr>
  <tr>
    <td>GO:0036503</td>
    <td>ERAD pathway</td>
  </tr>
  <tr>
    <td>GO:0043524</td>
    <td>negative regulation of neuron apoptotic process</td>
  </tr>
  <tr>
    <td>GO:0009888</td>
    <td>tissue development</td>
  </tr>
  <tr>
    <td>GO:0046165</td>
    <td>alcohol biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0010508</td>
    <td>positive regulation of autophagy</td>
  </tr>
  <tr>
    <td>GO:0071345</td>
    <td>cellular response to cytokine stimulus</td>
  </tr>
  <tr>
    <td>GO:0003006</td>
    <td>developmental process involved in reproduction</td>
  </tr>
  <tr>
    <td>GO:0044281</td>
    <td>small molecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0001659</td>
    <td>temperature homeostasis</td>
  </tr>
  <tr>
    <td>GO:0008643</td>
    <td>carbohydrate transport</td>
  </tr>
  <tr>
    <td>GO:0006694</td>
    <td>steroid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0097530</td>
    <td>granulocyte migration</td>
  </tr>
  <tr>
    <td>GO:0060538</td>
    <td>skeletal muscle organ development</td>
  </tr>
  <tr>
    <td>GO:0007009</td>
    <td>plasma membrane organization</td>
  </tr>
  <tr>
    <td>GO:0043112</td>
    <td>receptor metabolic process</td>
  </tr>
  <tr>
    <td>GO:0031214</td>
    <td>biomolecular tissue development</td>
  </tr>
  <tr>
    <td>GO:0050117</td>
    <td>actin filament bundle assembly</td>
  </tr>
  <tr>
    <td>GO:0061572</td>
    <td>actin filament bundle organization</td>
  </tr>
  <tr>
    <td>GO:0006633</td>
    <td>fatty acid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0034097</td>
    <td>response to cytokine</td>
  </tr>
  <tr>
    <td>GO:0046434</td>
    <td>organophosphate catabolic process</td>
  </tr>
  <tr>
    <td>GO:0110148</td>
    <td>biominalization</td>
  </tr>
  <tr>
    <td>GO:1901215</td>
    <td>negative regulation of neuron death</td>
  </tr>
  <tr>
    <td>GO:0030001</td>
    <td>metal ion transport</td>
  </tr>
  <tr>
    <td>GO:0043523</td>
    <td>regulation of neuron apoptotic process</td>
  </tr>
  <tr>
    <td>GO:0000910</td>
    <td>cytokinesis</td>
  </tr>
  <tr>
    <td>GO:0009267</td>
    <td>cellular response to starvation</td>
  </tr>
  <tr>
    <td>GO:0009894</td>
    <td>regulation of catabolic process</td>
  </tr>
  <tr>
    <td>GO:0019752</td>
    <td>carboxylic acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0051302</td>
    <td>regulation of cell division</td>
  </tr>
  <tr>
    <td>GO:0043436</td>
    <td>oxoacid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0006575</td>
    <td>cellular modified amino acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0031334</td>
    <td>positive regulation of protein-containing complex assembly</td>
  </tr>
  <tr>
    <td>GO:0006836</td>
    <td>neurotransmitter transport</td>
  </tr>
  <tr>
    <td>GO:0006082</td>
    <td>organic acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0072330</td>
    <td>monocarboxylic acid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0035725</td>
    <td>sodium ion transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0042594</td>
    <td>response to starvation</td>
  </tr>
  <tr>
    <td>GO:0009913</td>
    <td>epidermal cell differentiation</td>
  </tr>
  <tr>
    <td>GO:0019637</td>
    <td>organophosphate metabolic process</td>
  </tr>
  <tr>
    <td>GO:0031669</td>
    <td>cellular response to nutrient levels</td>
  </tr>
  <tr>
    <td>GO:0007033</td>
    <td>vacuole organization</td>
  </tr>
  <tr>
    <td>GO:0097529</td>
    <td>myeloid leukocyte migration</td>
  </tr>
  <tr>
    <td>GO:1902115</td>
    <td>regulation of organelle assembly</td>
  </tr>
  <tr>
    <td>GO:0051402</td>
    <td>neuron apoptotic process</td>
  </tr>
  <tr>
    <td>GO:0009060</td>
    <td> aerobic respiration</td>
  </tr>
  <tr>
    <td>GO:0042180</td>
    <td>cellular ketone metabolic process</td>
  </tr>
  <tr>
    <td>GO:0060348</td>
    <td>bone development</td>
  </tr>
  <tr>
    <td>GO:1901617</td>
    <td>organic hydroxy compound biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:1901575</td>
    <td>organic substance catabolic process</td>
  </tr>
  <tr>
    <td>GO:0044255</td>
    <td>cellular lipid metabolic process</td>
  </tr>
  <tr>
    <td>GO:1901212</td>
    <td>regulation of neuron death</td>
  </tr>
  <tr>
    <td>GO:0031668</td>
    <td>cellular response to extracellular stimulus</td>
  </tr>
</table>

<table>
  <tr>
    <td>The chemical reactions and pathways involving monocarb ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.43 2/470</td>
    <td>0,184241808</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving dicarboxyli IDH1</td>
    <td>7.14 1/14</td>
    <td>1.67 1/60</td>
    <td>0,184241808</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate ALPL</td>
    <td>7.14 1/14</td>
    <td>1.61 1/62</td>
    <td>0,187155616</td>
  </tr>
  <tr>
    <td>Behavior associated with the intake of food. CNTRF</td>
    <td>7.14 1/14</td>
    <td>1.59 1/63</td>
    <td>0,18802391</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents or reduces the frequency ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.45 1/69</td>
    <td>0,196879758</td>
  </tr>
  <tr>
    <td>The formation of a protein tetramer, a macromolecular str KRT10</td>
    <td>7.14 1/14</td>
    <td>1.45 1/69</td>
    <td>0,196879758</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>1.49 1/67</td>
    <td>0,196879758</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.45 1/69</td>
    <td>0,196879758</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.41 1/71</td>
    <td>0,198281792</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents, or reduces the frequency ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.41 1/71</td>
    <td>0,198281792</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.38 2/525</td>
    <td>0,202907868</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal ANXA7 ERLIN2 IDH1</td>
    <td>28.57 4/14</td>
    <td>0.19 4/210</td>
    <td>0,202907868</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>1.33 1/75</td>
    <td>0,202907868</td>
  </tr>
  <tr>
    <td>The process in which glucose is transported across a mem SLC5A9</td>
    <td>7.14 1/14</td>
    <td>1.27 1/79</td>
    <td>0,211341563</td>
  </tr>
  <tr>
    <td>The process in which bones are generated and organized. ALPL</td>
    <td>7.14 1/14</td>
    <td>1.20 1/83</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a BSPRY</td>
    <td>7.14 1/14</td>
    <td>1.18 1/85</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>The process in which hexose is transported across a memb SLC5A9</td>
    <td>7.14 1/14</td>
    <td>1.23 1/81</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>The series of steps necessary to target endoplasmic reticul ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.20 1/83</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>The directed movement of monocarboxylic acids into, out SLC6A8</td>
    <td>7.14 1/14</td>
    <td>1.18 1/85</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a BSPRY</td>
    <td>7.14 1/14</td>
    <td>1.19 1/84</td>
    <td>0,21422839</td>
  </tr>
  <tr>
    <td>The process in which a monosaccharide is transported acr SLC5A9</td>
    <td>7.14 1/14</td>
    <td>1.15 1/87</td>
    <td>0,217099264</td>
  </tr>
  <tr>
    <td>The process in which a carbohydrate is transported across SLC5A9</td>
    <td>7.14 1/14</td>
    <td>1.12 1/89</td>
    <td>0,217912025</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of ALPL BSPRY CNTRF</td>
    <td>28.57 4/14</td>
    <td>0.18 4/222</td>
    <td>0,217912025</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>1.09 1/92</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving cholesterol ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.04 1/96</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The process in which a relatively unspecialized cell acquire KRT10</td>
    <td>7.14 1/14</td>
    <td>1.05 1/95</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The deposition of hydroxyapatite, a form of calcium phosp ALPL</td>
    <td>7.14 1/14</td>
    <td>1.05 1/95</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>Any process that modulates the chemical reactions and pa ERLIN2</td>
    <td>7.14 1/14</td>
    <td>1.02 1/98</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent IDH1 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.33 2/613</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The process by which heat is generated by increasing meta ALPL</td>
    <td>7.14 1/14</td>
    <td>1.08 1/93</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The formation of a double membrane-bounded structure, SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>1.08 1/93</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The movement of a neutrophil within or between different GP2</td>
    <td>7.14 1/14</td>
    <td>1.04 1/96</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>A process that is carried out at the cellular level which resi SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>1.02 1/98</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or ALPL</td>
    <td>7.14 1/14</td>
    <td>1.08 1/93</td>
    <td>0,21798349</td>
  </tr>
  <tr>
    <td>The regulated production of heat in response to short tern ALPL</td>
    <td>7.14 1/14</td>
    <td>0.98 1/102</td>
    <td>0,22271412</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving sterols, ste ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.97 1/103</td>
    <td>0,22271412</td>
  </tr>
  <tr>
    <td>The protein catabolic pathway which targets endoplasmic ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.97 1/103</td>
    <td>0,22271412</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents, or reduces the frequency CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.96 1/104</td>
    <td>0,223005828</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of: ALPL ANXA7 KRT10</td>
    <td>21.43 3/14</td>
    <td>0.21 3/143</td>
    <td>0,229156697</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.92 1/109</td>
    <td>0,229677896</td>
  </tr>
  <tr>
    <td>Any process that activates, maintains or increases the rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.88 1/114</td>
    <td>0,231020925</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a BSPRY CNTRF</td>
    <td>14.29 2/14</td>
    <td>0.30 2/660</td>
    <td>0,231020925</td>
  </tr>
  <tr>
    <td>A developmental process in which a progressive change in ALPL CNTRF</td>
    <td>14.29 2/14</td>
    <td>0.30 2/666</td>
    <td>0,231020925</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving small mole ALPL ERLIN2 IDH1</td>
    <td>21.43 3/14</td>
    <td>0.21 3/146</td>
    <td>0,231020925</td>
  </tr>
  <tr>
    <td>A homeostatic process in which an organism modulates its ALPL</td>
    <td>7.14 1/14</td>
    <td>0.88 1/114</td>
    <td>0,231020925</td>
  </tr>
  <tr>
    <td>The directed movement of carbohydrate into, out of or wi SLC5A9</td>
    <td>7.14 1/14</td>
    <td>0.86 1/116</td>
    <td>0,231139951</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.86 1/116</td>
    <td>0,231139951</td>
  </tr>
  <tr>
    <td>The movement of a granulocyte within or between diffeire GP2</td>
    <td>7.14 1/14</td>
    <td>0.85 1/118</td>
    <td>0,233233916</td>
  </tr>
  <tr>
    <td>The progression of a skeletal muscle organ over time from CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.78 1/129</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>A process that is carried out at the cellular level which resi SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.80 1/125</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving a receptor SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.77 1/130</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>Formation of hard tissues that consist mainly of inorganic c ALPL</td>
    <td>7.14 1/14</td>
    <td>0.80 1/125</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The assembly of actin filament bundles; actin filaments are MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.79 1/126</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>A process that results in the assembly, arrangement of con MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.78 1/128</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.81 1/124</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a BSPRY CNTRF</td>
    <td>14.29 2/14</td>
    <td>0.28 2/713</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal IDH1</td>
    <td>7.14 1/14</td>
    <td>0.79 1/126</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The process where mineral crystals are formed and deposi ALPL</td>
    <td>7.14 1/14</td>
    <td>0.79 1/127</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents or reduces the frequency CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.77 1/130</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>The directed movement of metal ions, any metal ion with SLC5A9 SLC6A8</td>
    <td>14.29 2/14</td>
    <td>0.28 2/708</td>
    <td>0,23507163</td>
  </tr>
  <tr>
    <td>Any process that modulates the occurrence or rate of cell CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.76 1/132</td>
    <td>0,236923618</td>
  </tr>
  <tr>
    <td>The division of the cytoplasm and the plasma membrane o SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.75 1/134</td>
    <td>0,238746302</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.73 1/137</td>
    <td>0,23904417</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate, or extent IDH1 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.27 2/732</td>
    <td>0,23904417</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving carboxylic ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.27 2/736</td>
    <td>0,23904417</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.72 1/138</td>
    <td>0,239138704</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving any oxoaci ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.27 2/745</td>
    <td>0,240236722</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving compound IDH1</td>
    <td>7.14 1/14</td>
    <td>0.65 1/153</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.68 1/148</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>The directed movement of a neurotransmitter into, out of SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.67 1/149</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving organic aci ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.26 2/774</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.65 1/153</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>A process in which a sodium ion is transported from one si SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.67 1/149</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.66 1/151</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>The process in which a relatively unspecialized cell acquire KRT10</td>
    <td>7.14 1/14</td>
    <td>0.65 1/153</td>
    <td>0,24920429</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving organoph ALPL IDH1</td>
    <td>14.29 2/14</td>
    <td>0.25 2/793</td>
    <td>0,252377521</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.62 1/161</td>
    <td>0,256809463</td>
  </tr>
  <tr>
    <td>A process that is carried out at the cellular level which resi SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.62 1/160</td>
    <td>0,256809463</td>
  </tr>
  <tr>
    <td>The movement of a myeloid leukocyte within or between c GP2</td>
    <td>7.14 1/14</td>
    <td>0.60 1/166</td>
    <td>0,259641729</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.60 1/166</td>
    <td>0,259641729</td>
  </tr>
  <tr>
    <td>Any apoptotic process in a neuron, the basic cellular unit CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.61 1/164</td>
    <td>0,259641729</td>
  </tr>
  <tr>
    <td>The enzymatic release of energy from inorganic and organi IDH1</td>
    <td>7.14 1/14</td>
    <td>0.59 1/169</td>
    <td>0,262434639</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving any of a cl SLC ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.59 1/170</td>
    <td>0,262434639</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of I ALPL</td>
    <td>7.14 1/14</td>
    <td>0.57 1/175</td>
    <td>0,265045347</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.57 1/175</td>
    <td>0,265045347</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2 IDH1 SH3GL</td>
    <td>21.43 3/14</td>
    <td>0.17 3/174</td>
    <td>0,265045347</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving lipids, as cl ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.23 2/852</td>
    <td>0,266687742</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.56 1/179</td>
    <td>0,267663455</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.55 1/181</td>
    <td>0,268944706</td>
  </tr>
</table>
<table>
  <tr>
    <td>GO:0008654</td>
    <td>phospholipid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0060429</td>
    <td>epithelium development</td>
  </tr>
  <tr>
    <td>GO:0044242</td>
    <td>cellular lipid catabolic process</td>
  </tr>
  <tr>
    <td>GO:0016485</td>
    <td>protein processing</td>
  </tr>
  <tr>
    <td>GO:0048705</td>
    <td>skeletal system morphogenesis</td>
  </tr>
  <tr>
    <td>GO:0071310</td>
    <td>cellular response to organic substance</td>
  </tr>
  <tr>
    <td>GO:0007548</td>
    <td>sex differentiation</td>
  </tr>
  <tr>
    <td>GO:0045333</td>
    <td>cellular respiration</td>
  </tr>
  <tr>
    <td>GO:0016236</td>
    <td>macroautophagy</td>
  </tr>
  <tr>
    <td>GO:0051259</td>
    <td>protein complex oligomerization</td>
  </tr>
  <tr>
    <td>GO:0043587</td>
    <td>skin development</td>
  </tr>
  <tr>
    <td>GO:0070997</td>
    <td>neuron death</td>
  </tr>
  <tr>
    <td>GO:0071496</td>
    <td>cellular response to external stimulus</td>
  </tr>
  <tr>
    <td>GO:0007517</td>
    <td>muscle organ development</td>
  </tr>
  <tr>
    <td>GO:0051179</td>
    <td>localization</td>
  </tr>
  <tr>
    <td>GO:0008202</td>
    <td>steroid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0010506</td>
    <td>regulation of autophagy</td>
  </tr>
  <tr>
    <td>GO:0046942</td>
    <td>carboxylic acid transport</td>
  </tr>
  <tr>
    <td>GO:0044262</td>
    <td>cellular carbohydrate metabolic process</td>
  </tr>
  <tr>
    <td>GO:0034976</td>
    <td>response to endoplasmic reticulum stress</td>
  </tr>
  <tr>
    <td>GO:0071702</td>
    <td>organic substance transport</td>
  </tr>
  <tr>
    <td>GO:0006812</td>
    <td>cation transport</td>
  </tr>
  <tr>
    <td>GO:0008544</td>
    <td>epidermis development</td>
  </tr>
  <tr>
    <td>GO:0098656</td>
    <td>anion transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0062012</td>
    <td>regulation of small molecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0046394</td>
    <td>carboxylic acid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0016053</td>
    <td>organic acid biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0000003</td>
    <td>reproduction</td>
  </tr>
  <tr>
    <td>GO:0022414</td>
    <td>reproductive process</td>
  </tr>
  <tr>
    <td>GO:0051604</td>
    <td>protein maturation</td>
  </tr>
  <tr>
    <td>GO:0048856</td>
    <td>anatomical structure development</td>
  </tr>
  <tr>
    <td>GO:0006790</td>
    <td>sulfur compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0006979</td>
    <td>response to oxidative stress</td>
  </tr>
  <tr>
    <td>GO:0015980</td>
    <td>energy derivation by oxidation of organic compounds</td>
  </tr>
  <tr>
    <td>GO:0016042</td>
    <td>lipid catabolic process</td>
  </tr>
  <tr>
    <td>GO:0006629</td>
    <td>lipid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0001503</td>
    <td>ossification</td>
  </tr>
  <tr>
    <td>GO:0050900</td>
    <td>leukocyte migration</td>
  </tr>
  <tr>
    <td>GO:0009057</td>
    <td>macromolecule catabolic process</td>
  </tr>
  <tr>
    <td>GO:0015711</td>
    <td>organic anion transport</td>
  </tr>
  <tr>
    <td>GO:0006631</td>
    <td>fatty acid metabolic process</td>
  </tr>
  <tr>
    <td>GO:1901564</td>
    <td>organonitrogen compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0043254</td>
    <td>regulation of protein-containing complex assembly</td>
  </tr>
  <tr>
    <td>GO:0006644</td>
    <td>phospholipid metabolic process</td>
  </tr>
  <tr>
    <td>GO:0031331</td>
    <td>positive regulation of cellular catabolic process</td>
  </tr>
  <tr>
    <td>GO:0032502</td>
    <td>developmental process</td>
  </tr>
  <tr>
    <td>GO:0016192</td>
    <td>vesicle-mediated transport</td>
  </tr>
  <tr>
    <td>GO:0070887</td>
    <td>cellular response to chemical stimulus</td>
  </tr>
  <tr>
    <td>GO:0006915</td>
    <td>apoptotic process</td>
  </tr>
  <tr>
    <td>GO:0048871</td>
    <td>multicellular organismal homeostasis</td>
  </tr>
  <tr>
    <td>GO:0051301</td>
    <td>cell division</td>
  </tr>
  <tr>
    <td>GO:0048731</td>
    <td>system development</td>
  </tr>
  <tr>
    <td>GO:0071407</td>
    <td>cellular response to organic cyclic compound</td>
  </tr>
  <tr>
    <td>GO:0044089</td>
    <td>positive regulation of cellular component biogenesis</td>
  </tr>
  <tr>
    <td>GO:0043161</td>
    <td>proteasome-mediated ubiquitin-dependent protein catabolic process</td>
  </tr>
  <tr>
    <td>GO:0012501</td>
    <td>programmed cell death</td>
  </tr>
  <tr>
    <td>GO:0006091</td>
    <td>generation of precursor metabolites and energy</td>
  </tr>
  <tr>
    <td>GO:0006811</td>
    <td>ion transport</td>
  </tr>
  <tr>
    <td>GO:0009896</td>
    <td>positive regulation of catabolic process</td>
  </tr>
  <tr>
    <td>GO:0016311</td>
    <td>dephosphorylation</td>
  </tr>
  <tr>
    <td>GO:0007015</td>
    <td>actin filament organization</td>
  </tr>
  <tr>
    <td>GO:0010638</td>
    <td>positive regulation of organelle organization</td>
  </tr>
  <tr>
    <td>GO:0001501</td>
    <td>skeletal system development</td>
  </tr>
  <tr>
    <td>GO:0019221</td>
    <td>cytokine-mediated signaling pathway</td>
  </tr>
  <tr>
    <td>GO:0010256</td>
    <td>endomembrane system organization</td>
  </tr>
  <tr>
    <td>GO:0055085</td>
    <td>transmembrane transport</td>
  </tr>
  <tr>
    <td>GO:0007610</td>
    <td>behavior</td>
  </tr>
  <tr>
    <td>GO:0008219</td>
    <td>cell death</td>
  </tr>
  <tr>
    <td>GO:0044283</td>
    <td>small molecule biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0070727</td>
    <td>cellular macromolecule localization</td>
  </tr>
  <tr>
    <td>GO:0034613</td>
    <td>cellular protein localization</td>
  </tr>
  <tr>
    <td>GO:0090407</td>
    <td>organophosphate biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0033554</td>
    <td>cellular response to stress</td>
  </tr>
  <tr>
    <td>GO:0006820</td>
    <td>anion transport</td>
  </tr>
  <tr>
    <td>GO:0061061</td>
    <td>muscle structure development</td>
  </tr>
  <tr>
    <td>GO:0048513</td>
    <td>animal organ development</td>
  </tr>
  <tr>
    <td>GO:0006810</td>
    <td>transport</td>
  </tr>
  <tr>
    <td>GO:0006897</td>
    <td>endocytosis</td>
  </tr>
  <tr>
    <td>GO:0033993</td>
    <td>response to lipid</td>
  </tr>
  <tr>
    <td>GO:0010498</td>
    <td>proteasomal protein catabolic process</td>
  </tr>
  <tr>
    <td>GO:0007275</td>
    <td>multicellular organism development</td>
  </tr>
  <tr>
    <td>GO:0072657</td>
    <td>protein localization to membrane</td>
  </tr>
  <tr>
    <td>GO:0005975</td>
    <td>carbohydrate metabolic process</td>
  </tr>
  <tr>
    <td>GO:0014070</td>
    <td>response to organic cyclic compound</td>
  </tr>
  <tr>
    <td>GO:0051234</td>
    <td>establishment of localization</td>
  </tr>
  <tr>
    <td>GO:0071705</td>
    <td>nitrogen compound transport</td>
  </tr>
  <tr>
    <td>GO:0010564</td>
    <td>regulation of cell cycle process</td>
  </tr>
  <tr>
    <td>GO:0042221</td>
    <td>response to chemical</td>
  </tr>
  <tr>
    <td>GO:0006950</td>
    <td>response to stress</td>
  </tr>
</table>

<table>
  <tr>
    <td>The chemical reactions and pathways resulting in the form IDH1</td>
    <td>7.14 1/14</td>
    <td>0.54 1/185</td>
    <td>0,272499475</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : ANXA7 KRT10</td>
    <td>14.29 2/14</td>
    <td>0.23 2/874</td>
    <td>0,272499475</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal IDH1</td>
    <td>7.14 1/14</td>
    <td>0.53 1/188</td>
    <td>0,274051847</td>
  </tr>
  <tr>
    <td>Any protein maturation process achieved by the cleavage &lt;CD5L</td>
    <td>7.14 1/14</td>
    <td>0.52 1/192</td>
    <td>0,277973286</td>
  </tr>
  <tr>
    <td>The process in which the anatomical structures of the skeli ALPL</td>
    <td>7.14 1/14</td>
    <td>0.50 1/199</td>
    <td>0,285877842</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL BSPRY CNTRF</td>
    <td>21.43 3/14</td>
    <td>0.16 3/184</td>
    <td>0,287438919</td>
  </tr>
  <tr>
    <td>The establishment of the sex of an organism by physical di CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.49 1/205</td>
    <td>0,288890774</td>
  </tr>
  <tr>
    <td>The enzymatic release of energy from inorganic and organi IDH1</td>
    <td>7.14 1/14</td>
    <td>0.49 1/206</td>
    <td>0,288890774</td>
  </tr>
  <tr>
    <td>The major inducible pathway for the general turnover of &lt; c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.49 1/205</td>
    <td>0,288890774</td>
  </tr>
  <tr>
    <td>The process of creating protein oligomers, compounds cor KRT10</td>
    <td>7.14 1/14</td>
    <td>0.48 1/209</td>
    <td>0,291243947</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : I KRT10</td>
    <td>7.14 1/14</td>
    <td>0.47 1/212</td>
    <td>0,293286893</td>
  </tr>
  <tr>
    <td>The process of cell death in a neuron. CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.47 1/213</td>
    <td>0,293286893</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.45 1/222</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : I CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.45 1/224</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>Any process in which a cell, a substance, or a cellular enti: CD5L GP2 NAPA SH: 42.86 6/14</td>
    <td>0.11 6/541</td>
    <td>0,301249335</td>
    <td></td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving steroids, cc ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.44 1/229</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent &lt; c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.44 1/229</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>The directed movement of carboxylic acids into, out of or &lt; SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.44 1/228</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving carbohydrz IDH1</td>
    <td>7.14 1/14</td>
    <td>0.44 1/229</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.45 1/224</td>
    <td>0,301249335</td>
  </tr>
  <tr>
    <td>The directed movement of organic substances into, out of NAPA SLC5A9 SLC6A8</td>
    <td>21.43 3/14</td>
    <td>0.15 3/196</td>
    <td>0,301725763</td>
  </tr>
  <tr>
    <td>The directed movement of cations, atoms or small molecu: SLC5A9 SLC6A8</td>
    <td>14.29 2/14</td>
    <td>0.20 2/999</td>
    <td>0,301725763</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : I KRT10</td>
    <td>7.14 1/14</td>
    <td>0.42 1/236</td>
    <td>0,301725763</td>
  </tr>
  <tr>
    <td>The process in which an anion is transported across a merr SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.43 1/232</td>
    <td>0,301725763</td>
  </tr>
  <tr>
    <td>Any process that modulates the rate, frequency or extent &lt; ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.42 1/236</td>
    <td>0,301725763</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.42 1/239</td>
    <td>0,303759134</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.41 1/242</td>
    <td>0,305746757</td>
  </tr>
  <tr>
    <td>The production of new individuals that contain some porti ALPL CNTRF</td>
    <td>14.29 2/14</td>
    <td>0.20 2/102</td>
    <td>0,305746757</td>
  </tr>
  <tr>
    <td>A biological process that directly contributes to the proces ALPL CNTRF</td>
    <td>14.29 2/14</td>
    <td>0.20 2/102</td>
    <td>0,305746757</td>
  </tr>
  <tr>
    <td>Any process leading to the attainment of the full functiona CD5L</td>
    <td>7.14 1/14</td>
    <td>0.39 1/254</td>
    <td>0,315052273</td>
  </tr>
  <tr>
    <td>The biological process whose specific outcome is the progr ALPL ANXA7 CNTRF</td>
    <td>35.71 5/14</td>
    <td>0.11 5/437</td>
    <td>0,32699463</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving the nonme IDH1</td>
    <td>7.14 1/14</td>
    <td>0.37 1/272</td>
    <td>0,332234638</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a IDH1</td>
    <td>7.14 1/14</td>
    <td>0.36 1/275</td>
    <td>0,333974491</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways by which a cell deriv IDH1</td>
    <td>7.14 1/14</td>
    <td>0.36 1/280</td>
    <td>0,337892402</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal IDH1</td>
    <td>7.14 1/14</td>
    <td>0.35 1/284</td>
    <td>0,34066382</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving lipids, com ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.18 2/112</td>
    <td>0,341261655</td>
  </tr>
  <tr>
    <td>The formation of bone or of a bony substance, or the conv ALPL</td>
    <td>7.14 1/14</td>
    <td>0.35 1/289</td>
    <td>0,341261655</td>
  </tr>
  <tr>
    <td>The movement of a leukocyte within or between different GP2</td>
    <td>7.14 1/14</td>
    <td>0.35 1/289</td>
    <td>0,341261655</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.18 2/114</td>
    <td>0,346305827</td>
  </tr>
  <tr>
    <td>The directed movement of organic anions into, out of or w SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.33 1/306</td>
    <td>0,356072443</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving fatty acids, ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.32 1/316</td>
    <td>0,364860904</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving organonitri ALPL BSPRY CD5L EF 42.86 6/14</td>
    <td>0.10 6/591</td>
    <td>0,373962119</td>
    <td></td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent &lt; c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.30 1/330</td>
    <td>0,37588299</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving phospholip IDH1</td>
    <td>7.14 1/14</td>
    <td>0.30 1/338</td>
    <td>0,38228067</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.29 1/342</td>
    <td>0,384569779</td>
  </tr>
  <tr>
    <td>A biological process whose specific outcome is the progr ALPL ANXA7 CNTRF</td>
    <td>35.71 5/14</td>
    <td>0.11 5/4757</td>
    <td>0,394007027</td>
  </tr>
  <tr>
    <td>A cellular transport process in which transported substanc CD5L NAPA</td>
    <td>14.29 2/14</td>
    <td>0.16 2/127</td>
    <td>0,395703715</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL BSPRY CNTRF</td>
    <td>21.43 3/14</td>
    <td>0.13 3/237</td>
    <td>0,398667135</td>
  </tr>
  <tr>
    <td>A programmed cell death process which begins when a cel CNTRF SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.15 2/129</td>
    <td>0,402320032</td>
  </tr>
  <tr>
    <td>Any process involved in the maintenance of an internal ste ALPL</td>
    <td>7.14 1/14</td>
    <td>0.27 1/369</td>
    <td>0,402320032</td>
  </tr>
  <tr>
    <td>The process resulting in division and partitioning of compo SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.27 1/373</td>
    <td>0,40438132</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : I ALPL CNTRF KRT10</td>
    <td>12.857 4/14</td>
    <td>0.11 4/361</td>
    <td>0,408178997</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL</td>
    <td>7.14 1/14</td>
    <td>0.26 1/383</td>
    <td>0,408522312</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.26 1/382</td>
    <td>0,408522312</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.26 1/391</td>
    <td>0,408898892</td>
  </tr>
  <tr>
    <td>A process which begins when a cell receives an internal or CNTRF SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.15 2/134</td>
    <td>0,408898892</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form IDH1</td>
    <td>7.14 1/14</td>
    <td>0.26 1/386</td>
    <td>0,408898892</td>
  </tr>
  <tr>
    <td>The directed movement of charged atoms or small charge: SLC5A9 SLC6A8</td>
    <td>14.29 2/14</td>
    <td>0.15 2/134</td>
    <td>0,408898892</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.25 1/400</td>
    <td>0,410121831</td>
  </tr>
  <tr>
    <td>The process of removing one or more phosphoric (ester or ALPL</td>
    <td>7.14 1/14</td>
    <td>0.25 1/399</td>
    <td>0,410121831</td>
  </tr>
  <tr>
    <td>A process that is carried out at the cellular level which res: MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.25 1/396</td>
    <td>0,410121831</td>
  </tr>
  <tr>
    <td>Any process that increases the frequency, rate or extent of SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.25 1/398</td>
    <td>0,410121831</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of : I ALPL</td>
    <td>7.14 1/14</td>
    <td>0.25 1/405</td>
    <td>0,412863711</td>
  </tr>
  <tr>
    <td>A series of molecular signals initiated by the binding of a &lt; c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.25 1/408</td>
    <td>0,412963669</td>
  </tr>
  <tr>
    <td>A process that is carried out at the cellular level which res: SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.24 1/409</td>
    <td>0,412963669</td>
  </tr>
  <tr>
    <td>The process in which a solute is transported across a lipid I SLC5A9 SLC6A8</td>
    <td>14.29 2/14</td>
    <td>0.14 2/140</td>
    <td>0,420001124</td>
  </tr>
  <tr>
    <td>The internally coordinated responses (actions or inactions) CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.14 2/421</td>
    <td>0,420001124</td>
  </tr>
  <tr>
    <td>Any biological process that results in permanent cessation CNTRF SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.14 2/143</td>
    <td>0,42672106</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.23 1/437</td>
    <td>0,42672106</td>
  </tr>
  <tr>
    <td>Any process in which a macromolecule is transported to, a NAPA SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.14 2/1431</td>
    <td>0,42672106</td>
  </tr>
  <tr>
    <td>Any process in which a protein is transported to, and/or m NAPA SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.14 2/143</td>
    <td>0,42672106</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the bios IDH1</td>
    <td>7.14 1/14</td>
    <td>0.23 1/439</td>
    <td>0,42672106</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ERLIN2 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.14 2/146</td>
    <td>0,428211624</td>
  </tr>
  <tr>
    <td>The directed movement of anions, atoms or small molecu: SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.22 1/449</td>
    <td>0,428211624</td>
  </tr>
  <tr>
    <td>The progression of a muscle structure over time, from its f CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.22 1/445</td>
    <td>0,428211624</td>
  </tr>
  <tr>
    <td>Development of a tissue or tissues that work together to p ALPL CNTRF KRT10</td>
    <td>21.43 3/14</td>
    <td>0.11 3/261</td>
    <td>0,428211624</td>
  </tr>
  <tr>
    <td>The directed movement of substances (such as macromole CD5L NAPA SLC5A9</td>
    <td>28.57 4/14</td>
    <td>0.10 4/388</td>
    <td>0,433436809</td>
  </tr>
  <tr>
    <td>A vesicle-mediated transport process in which cells take ur CD5L</td>
    <td>7.14 1/14</td>
    <td>0.21 1/466</td>
    <td>0,433436809</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL</td>
    <td>7.14 1/14</td>
    <td>0.22 1/464</td>
    <td>0,433436809</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.22 1/464</td>
    <td>0,433436809</td>
  </tr>
  <tr>
    <td>The biological process whose specific outcome is the progr ALPL CNTRF KRT10</td>
    <td>12.857 4/14</td>
    <td>0.10 4/387</td>
    <td>0,433436809</td>
  </tr>
  <tr>
    <td>A process in which a protein is transported to, or maintain SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.21 1/473</td>
    <td>0,437287783</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving carbohydrz IDH1</td>
    <td>7.14 1/14</td>
    <td>0.21 1/484</td>
    <td>0,444205924</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL</td>
    <td>7.14 1/14</td>
    <td>0.20 1/495</td>
    <td>0,451008587</td>
  </tr>
  <tr>
    <td>Any process that localizes a substance or cellular compone: CD5L NAPA SLC5A9</td>
    <td>28.57 4/14</td>
    <td>0.10 4/403</td>
    <td>0,462048459</td>
  </tr>
  <tr>
    <td>The directed movement of nitrogen-containing compound NAPA SLC6A8</td>
    <td>14.29 2/14</td>
    <td>0.13 2/158</td>
    <td>0,462048459</td>
  </tr>
  <tr>
    <td>Any process that modulates a cellular process that is invol SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.19 1/520</td>
    <td>0,463737395</td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ALPL BSPRY CNTRF I 28.57 4/14</td>
    <td>0.10 4/405</td>
    <td>0,463737395</td>
    <td></td>
  </tr>
  <tr>
    <td>Any process that results in a change in state or activity of a ERLIN2 IDH1 SH3GL</td>
    <td>21.43 3/14</td>
    <td>0.11 3/280</td>
    <td>0,465301685</td>
  </tr>
</table>
<table>
  <tr>
    <td>GO:0051668</td>
    <td>localization within membrane</td>
    <td>Any process in which a substance or cellular entity, such as SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.18 1/541</td>
    <td>0.474974404</td>
  </tr>
  <tr>
    <td>GO:0006508</td>
    <td>proteolysis</td>
    <td>The hydrolysis of proteins into smaller polypeptides and/o CD5L ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.12 2/167</td>
    <td>0.487900758</td>
  </tr>
  <tr>
    <td>GO:0006511</td>
    <td>ubiquitin-dependent protein catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.17 1/589</td>
    <td>0.505700048</td>
  </tr>
  <tr>
    <td>GO:0019941</td>
    <td>modification-dependent protein catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.17 1/603</td>
    <td>0.513574642</td>
  </tr>
  <tr>
    <td>GO:0043632</td>
    <td>modification-dependent macromolecule catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.16 1/611</td>
    <td>0.515276864</td>
  </tr>
  <tr>
    <td>GO:0030036</td>
    <td>actin cytoskeleton organization</td>
    <td>A process that is carried out at the cellular level which resi MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.16 1/611</td>
    <td>0.515276864</td>
  </tr>
  <tr>
    <td>GO:0061024</td>
    <td>membrane organization</td>
    <td>A process which results in the assembly, arrangement of α SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.16 1/620</td>
    <td>0.519503943</td>
  </tr>
  <tr>
    <td>GO:0097435</td>
    <td>supramolecular fiber organization</td>
    <td>A process that is carried out at the cellular level which resi MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.16 1/636</td>
    <td>0.528353733</td>
  </tr>
  <tr>
    <td>GO:0007417</td>
    <td>central nervous system development</td>
    <td>The process whose specific outcome is the progression of MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.15 1/649</td>
    <td>0.532479195</td>
  </tr>
  <tr>
    <td>GO:0008284</td>
    <td>positive regulation of cell population proliferation</td>
    <td>Any process that activates or increases the rate or extent c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.15 1/651</td>
    <td>0.532479195</td>
  </tr>
  <tr>
    <td>GO:0043066</td>
    <td>negative regulation of apoptotic process</td>
    <td>Any process that stops, prevents, or reduces the frequency c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.15 1/640</td>
    <td>0.532479195</td>
  </tr>
  <tr>
    <td>GO:0010243</td>
    <td>response to organonitrogen compound</td>
    <td>Any process that results in a change in state or activity of a ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.15 1/658</td>
    <td>0.535111914</td>
  </tr>
  <tr>
    <td>GO:0043069</td>
    <td>negative regulation of programmed cell death</td>
    <td>Any process that stops, prevents, or reduces the frequency c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.15 1/663</td>
    <td>0.536415959</td>
  </tr>
  <tr>
    <td>GO:0098662</td>
    <td>inorganic cation transmembrane transport</td>
    <td>A process in which an inorganic cation is transported from SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.15 1/673</td>
    <td>0.540234846</td>
  </tr>
  <tr>
    <td>GO:0030029</td>
    <td>actin filament-based process</td>
    <td>Any cellular process that depends upon or alters the actin MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.15 1/675</td>
    <td>0.540234846</td>
  </tr>
  <tr>
    <td>GO:0051603</td>
    <td>proteolysis involved in cellular protein catabolic process</td>
    <td>The hydrolysis of a peptide bond or bonds within a protein ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.14 1/696</td>
    <td>0.551506482</td>
  </tr>
  <tr>
    <td>GO:0016567</td>
    <td>protein ubiquitination</td>
    <td>The process in which one or more ubiquitin groups are adv BSPRY</td>
    <td>7.14 1/14</td>
    <td>0.14 1/702</td>
    <td>0.553273348</td>
  </tr>
  <tr>
    <td>GO:0060548</td>
    <td>negative regulation of cell death</td>
    <td>Any process that decreases the rate or frequency of cell de CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.14 1/719</td>
    <td>0.56174767</td>
  </tr>
  <tr>
    <td>GO:0098660</td>
    <td>inorganic ion transmembrane transport</td>
    <td>The process in which an inorganic ion is transported across: SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.14 1/736</td>
    <td>0.562127217</td>
  </tr>
  <tr>
    <td>GO:0044257</td>
    <td>cellular protein catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.14 1/732</td>
    <td>0.562127217</td>
  </tr>
  <tr>
    <td>GO:0008104</td>
    <td>protein localization</td>
    <td>Any process in which a protein is transported to, or maintain NAPA SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.10 2/196</td>
    <td>0.562127217</td>
  </tr>
  <tr>
    <td>GO:0033365</td>
    <td>protein localization to organelle</td>
    <td>A process in which a protein is transported to, or maintain SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.14 1/729</td>
    <td>0.562127217</td>
  </tr>
  <tr>
    <td>GO:0019222</td>
    <td>regulation of metabolic process</td>
    <td>Any process that modulates the frequency, rate or extent c ALPL ANXA7 ERLIN2</td>
    <td>35.71 5/14</td>
    <td>0.08 5/597</td>
    <td>0.562127217</td>
  </tr>
  <tr>
    <td>GO:1901698</td>
    <td>response to nitrogen compound</td>
    <td>Any process that results in a change in state or activity of a ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.13 1/741</td>
    <td>0.562360499</td>
  </tr>
  <tr>
    <td>GO:0006886</td>
    <td>intracellular protein transport</td>
    <td>The directed movement of proteins in a cell, including the NAPA</td>
    <td>7.14 1/14</td>
    <td>0.13 1/743</td>
    <td>0.562360499</td>
  </tr>
  <tr>
    <td>GO:0009605</td>
    <td>response to external stimulus</td>
    <td>Any process that results in a change in state or activity of a ALPL SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.10 2/200</td>
    <td>0.565704898</td>
  </tr>
  <tr>
    <td>GO:0044087</td>
    <td>regulation of cellular component biogenesis</td>
    <td>Any process that modulates the frequency, rate or extent c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.13 1/762</td>
    <td>0.566188013</td>
  </tr>
  <tr>
    <td>GO:0032446</td>
    <td>protein modification by small protein conjugation</td>
    <td>A protein modification process in which one or more grou BSPRY</td>
    <td>7.14 1/14</td>
    <td>0.13 1/758</td>
    <td>0.566188013</td>
  </tr>
  <tr>
    <td>GO:0051130</td>
    <td>positive regulation of cellular component organization</td>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.13 1/763</td>
    <td>0.566188013</td>
  </tr>
  <tr>
    <td>GO:0070925</td>
    <td>organelle assembly</td>
    <td>The aggregation, arrangement and bonding together of a s SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.13 1/786</td>
    <td>0.577235731</td>
  </tr>
  <tr>
    <td>GO:0051726</td>
    <td>regulation of cell cycle</td>
    <td>Any process that modulates the rate or extent of progress SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.13 1/790</td>
    <td>0.577512781</td>
  </tr>
  <tr>
    <td>GO:0098655</td>
    <td>cation transmembrane transport</td>
    <td>The process in which a cation is transported across a mem SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.13 1/794</td>
    <td>0.577781997</td>
  </tr>
  <tr>
    <td>GO:0009887</td>
    <td>animal organ morphogenesis</td>
    <td>Morphogenesis of an animal organ. An organ is defined as ALPL</td>
    <td>7.14 1/14</td>
    <td>0.12 1/817</td>
    <td>0.588414518</td>
  </tr>
  <tr>
    <td>GO:0030163</td>
    <td>protein catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.12 1/855</td>
    <td>0.606726245</td>
  </tr>
  <tr>
    <td>GO:0070647</td>
    <td>protein modification by small protein conjugation or rem</td>
    <td>A protein modification process in which one or more grou BSPRY</td>
    <td>7.14 1/14</td>
    <td>0.11 1/877</td>
    <td>0.616170698</td>
  </tr>
  <tr>
    <td>GO:0006518</td>
    <td>peptide metabolic process</td>
    <td>The chemical reactions and pathways involving peptides, c IDH1</td>
    <td>7.14 1/14</td>
    <td>0.11 1/897</td>
    <td>0.624366921</td>
  </tr>
  <tr>
    <td>GO:0033043</td>
    <td>regulation of organelle organization</td>
    <td>Any process that modulates the frequency, rate or extent c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.11 1/903</td>
    <td>0.62533545</td>
  </tr>
  <tr>
    <td>GO:0022607</td>
    <td>cellular component assembly</td>
    <td>The aggregation, arrangement and bonding together of a c KRT10 MARCKS SH3 21.43 3/14</td>
    <td>0.08 3/366</td>
    <td>0.634395658</td>
    <td></td>
  </tr>
  <tr>
    <td>GO:0019538</td>
    <td>protein metabolic process</td>
    <td>The chemical reactions and pathways involving a protein. I BSPRY CD5L ERLIN2</td>
    <td>0.08 4/510</td>
    <td>0.645112565</td>
    <td></td>
  </tr>
  <tr>
    <td>GO:0022402</td>
    <td>cell cycle process</td>
    <td>The cellular process that ensures successive accurate and c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.10 1/965</td>
    <td>0.649542338</td>
  </tr>
  <tr>
    <td>GO:0044265</td>
    <td>cellular macromolecule catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.10 1/985</td>
    <td>0.652646283</td>
  </tr>
  <tr>
    <td>GO:0050896</td>
    <td>response to stimulus</td>
    <td>Any process that results in a change in state or activity of a ALPL BSPRY CNTRF</td>
    <td>14.28 6/14</td>
    <td>0.08 6/797</td>
    <td>0.652646283</td>
  </tr>
  <tr>
    <td>GO:0033036</td>
    <td>macromolecule localization</td>
    <td>Any process in which a macromolecule is transported to, o NAPA SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.08 2/236</td>
    <td>0.652646283</td>
  </tr>
  <tr>
    <td>GO:0006796</td>
    <td>phosphate-containing compound metabolic process</td>
    <td>The chemical reactions and pathways involving the phosph ALPL IDH1</td>
    <td>14.29 2/14</td>
    <td>0.08 2/240</td>
    <td>0.657397925</td>
  </tr>
  <tr>
    <td>GO:0034220</td>
    <td>ion transmembrane transport</td>
    <td>A process in which an ion is transported across a membr SLC6A8</td>
    <td>7.14 1/14</td>
    <td>0.10 1/100</td>
    <td>0.657397925</td>
  </tr>
  <tr>
    <td>GO:0051240</td>
    <td>positive regulation of multicellular organismal process</td>
    <td>Any process that activates or increases the frequency, rate ALPL</td>
    <td>7.14 1/14</td>
    <td>0.10 1/102</td>
    <td>0.659059358</td>
  </tr>
  <tr>
    <td>GO:0006793</td>
    <td>phosphorus metabolic process</td>
    <td>The chemical reactions and pathways involving the nonme ALPL IDH1</td>
    <td>14.29 2/14</td>
    <td>0.08 2/242</td>
    <td>0.659059358</td>
  </tr>
  <tr>
    <td>GO:0051641</td>
    <td>cellular localization</td>
    <td>A cellular localization process whereby a substance or cells NAPA SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.08 2/241</td>
    <td>0.659059358</td>
  </tr>
  <tr>
    <td>GO:1901700</td>
    <td>response to oxygen-containing compound</td>
    <td>Any process that results in a change in state or activity of a ALPL</td>
    <td>7.14 1/14</td>
    <td>0.10 1/102</td>
    <td>0.659642725</td>
  </tr>
  <tr>
    <td>GO:0044260</td>
    <td>cellular macromolecule metabolic process</td>
    <td>The chemical reactions and pathways involving macromole BSPRY ERLIN2 KRT1</td>
    <td>28.57 4/14</td>
    <td>0.08 4/530</td>
    <td>0.661370354</td>
  </tr>
  <tr>
    <td>GO:0042981</td>
    <td>regulation of apoptotic process</td>
    <td>Any process that modulates the occurrence or rate of cell c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.10 1/103</td>
    <td>0.661370354</td>
  </tr>
  <tr>
    <td>GO:0010629</td>
    <td>negative regulation of gene expression</td>
    <td>Any process that decreases the frequency, rate or extent o ANXA7</td>
    <td>7.14 1/14</td>
    <td>0.10 1/104</td>
    <td>0.661370354</td>
  </tr>
  <tr>
    <td>GO:0044085</td>
    <td>cellular component biogenesis</td>
    <td>A process that results in the biosynthesis of constituent m KRT10 MARCKS SH3 21.43 3/14</td>
    <td>0.08 3/390</td>
    <td>0.663732525</td>
    <td></td>
  </tr>
  <tr>
    <td>GO:0043067</td>
    <td>regulation of programmed cell death</td>
    <td>Any process that modulates the frequency, rate or extent c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.09 1/106</td>
    <td>0.665348444</td>
  </tr>
  <tr>
    <td>GO:0065003</td>
    <td>protein-containing complex assembly</td>
    <td>The aggregation, arrangement and bonding together of a s KRT10 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.08 2/252</td>
    <td>0.670212347</td>
  </tr>
  <tr>
    <td>GO:0019220</td>
    <td>regulation of phosphate metabolic process</td>
    <td>Any process that modulates the frequency, rate or extent c IDH1</td>
    <td>7.14 1/14</td>
    <td>0.09 1/109</td>
    <td>0.67133047</td>
  </tr>
  <tr>
    <td>GO:0051174</td>
    <td>regulation of phosphorus metabolic process</td>
    <td>Any process that modulates the frequency, rate or extent c IDH1</td>
    <td>7.14 1/14</td>
    <td>0.09 1/109</td>
    <td>0.67133047</td>
  </tr>
  <tr>
    <td>GO:0043603</td>
    <td>cellular amide metabolic process</td>
    <td>The chemical reactions and pathways involving an amide, c IDH1</td>
    <td>7.14 1/14</td>
    <td>0.09 1/111</td>
    <td>0.676669002</td>
  </tr>
  <tr>
    <td>GO:0051716</td>
    <td>cellular response to stimulus</td>
    <td>Any process that results in a change in state or activity of a ALPL BSPRY CNTRF</td>
    <td>35.71 5/14</td>
    <td>0.07 5/687</td>
    <td>0.67838709</td>
  </tr>
  <tr>
    <td>GO:1901565</td>
    <td>organonitrogen compound catabolic process</td>
    <td>The chemical reactions and pathways resulting in the breal ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.09 1121</td>
    <td>0.679383777</td>
  </tr>
  <tr>
    <td>GO:0010941</td>
    <td>regulation of cell death</td>
    <td>Any process that modulates the rate or frequency of cell d CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.09 1114</td>
    <td>0.682490344</td>
  </tr>
  <tr>
    <td>GO:0042127</td>
    <td>regulation of cell population proliferation</td>
    <td>Any process that modulates the frequency, rate or extent c CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.09 1115</td>
    <td>0.685924626</td>
  </tr>
  <tr>
    <td>GO:0043933</td>
    <td>protein-containing complex organization</td>
    <td>Any process in which macromolecules aggregate, disaggrej KRT10 SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.07 2/267</td>
    <td>0.69600714</td>
  </tr>
  <tr>
    <td>GO:0015031</td>
    <td>protein transport</td>
    <td>The directed movement of proteins into, out of or within a NAPA</td>
    <td>7.14 1/14</td>
    <td>0.08 1/119</td>
    <td>0.69600714</td>
  </tr>
  <tr>
    <td>GO:0016477</td>
    <td>cell migration</td>
    <td>The controlled self-propelled movement of a cell from one GP2</td>
    <td>7.14 1/14</td>
    <td>0.08 1/120</td>
    <td>0.697300013</td>
  </tr>
  <tr>
    <td>GO:0009892</td>
    <td>negative regulation of metabolic process</td>
    <td>Any process that stops, prevents, or reduces the frequency c ANXA7 ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.07 2/270</td>
    <td>0.697698405</td>
  </tr>
  <tr>
    <td>GO:0007010</td>
    <td>cytoskeleton organization</td>
    <td>A process that is carried out at the cellular level which resi MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.08 1/124</td>
    <td>0.70896947</td>
  </tr>
  <tr>
    <td>GO:0031327</td>
    <td>negative regulation of cellular biosynthetic process</td>
    <td>Any process that stops, prevents, or reduces the frequency c ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.08 1/125</td>
    <td>0.711891578</td>
  </tr>
  <tr>
    <td>GO:0009890</td>
    <td>negative regulation of biosynthetic process</td>
    <td>Any process that stops, prevents, or reduces the rate of th ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.08 1/127</td>
    <td>0.716163988</td>
  </tr>
  <tr>
    <td>GO:0045184</td>
    <td>establishment of protein localization</td>
    <td>The directed movement of a protein to a specific location. NAPA</td>
    <td>7.14 1/14</td>
    <td>0.08 1/128</td>
    <td>0.717188907</td>
  </tr>
  <tr>
    <td>GO:0007049</td>
    <td>cell cycle</td>
    <td>The progression of biochemical and morphological phases SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.08 1/130</td>
    <td>0.721647353</td>
  </tr>
  <tr>
    <td>GO:0042592</td>
    <td>homeostatic process</td>
    <td>Any biological process involved in the maintenance of an ir ALPL</td>
    <td>7.14 1/14</td>
    <td>0.07 1/135</td>
    <td>0.728911121</td>
  </tr>
  <tr>
    <td>GO:0046907</td>
    <td>intracellular transport</td>
    <td>The directed movement of substances within a cell. NAPA</td>
    <td>7.14 1/14</td>
    <td>0.07 1/133</td>
    <td>0.728911121</td>
  </tr>
  <tr>
    <td>GO:0051674</td>
    <td>localization of cell</td>
    <td>Any process in which a cell is transported to, and/or maint GP2</td>
    <td>7.14 1/14</td>
    <td>0.07 1/135</td>
    <td>0.728911121</td>
  </tr>
  <tr>
    <td>GO:0048870</td>
    <td>cell motility</td>
    <td>Any process involved in the controlled self-propelled move GP2</td>
    <td>7.14 1/14</td>
    <td>0.07 1/135</td>
    <td>0.728911121</td>
  </tr>
  <tr>
    <td>GO:0044267</td>
    <td>cellular protein metabolic process</td>
    <td>The chemical reactions and pathways involving a specific p BSPRY ERLIN2 KRT1</td>
    <td>21.43 3/14</td>
    <td>0.07 3/446</td>
    <td>0.735627158</td>
  </tr>
  <tr>
    <td>GO:0008283</td>
    <td>cell population proliferation</td>
    <td>The multiplication or reproduction of cells, resulting in the CNTRF</td>
    <td>7.14 1/14</td>
    <td>0.07 1/140</td>
    <td>0.742970078</td>
  </tr>
  <tr>
    <td>GO:0048519</td>
    <td>negative regulation of biological process</td>
    <td>Any process that stops, prevents, or reduces the frequency c ANXA7 CNTRF ERLIN2</td>
    <td>14.23 3/14</td>
    <td>0.07 3/454</td>
    <td>0.747280672</td>
  </tr>
  <tr>
    <td>GO:0009893</td>
    <td>positive regulation of metabolic process</td>
    <td>Any process that activates or increases the frequency, rate ALPL SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.07 2/304</td>
    <td>0.749650637</td>
  </tr>
  <tr>
    <td>GO:0040011</td>
    <td>locomotion</td>
    <td>Self-propelled movement of a cell or organism from one lo GP2</td>
    <td>7.14 1/14</td>
    <td>0.07 1/147</td>
    <td>0.7569576</td>
  </tr>
  <tr>
    <td>GO:0030154</td>
    <td>cell differentiation</td>
    <td>The process in which relatively unspecialized cells, e.g. eml ANXA7 KRT10</td>
    <td>14.29 2/14</td>
    <td>0.06 2/309</td>
    <td>0.75795121</td>
  </tr>
  <tr>
    <td>GO:0048869</td>
    <td>cellular developmental process</td>
    <td>A biological process whose specific outcome is the progres ANXA7 KRT10</td>
    <td>14.29 2/14</td>
    <td>0.06 2/316</td>
    <td>0.769346524</td>
  </tr>
  <tr>
    <td>GO:0006464</td>
    <td>cellular protein modification process</td>
    <td>The covalent alteration of one or more amino acids occur BSPRY KRT10</td>
    <td>14.29 2/14</td>
    <td>0.06 2/323</td>
    <td>0.780132201</td>
  </tr>
  <tr>
    <td>GO:0036211</td>
    <td>protein modification process</td>
    <td>The covalent alteration of one or more amino acids occur BSPRY KRT10</td>
    <td>14.29 2/14</td>
    <td>0.06 2/323</td>
    <td>0.780132201</td>
  </tr>
  <tr>
    <td>GO:0032501</td>
    <td>multicellular organismal process</td>
    <td>Any biological process, occurring at the level of a multicelli ALPL CNTRF KRT10</td>
    <td>12.857 4/14</td>
    <td>0.06 4/639</td>
    <td>0.793981459</td>
  </tr>
  <tr>
    <td>GO:0006996</td>
    <td>organelle organization</td>
    <td>A process that is carried out at the cellular level which resi MARCKS SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.06 2/333</td>
    <td>0.794239542</td>
  </tr>
  <tr>
    <td>GO:0051128</td>
    <td>regulation of cellular component organization</td>
    <td>Any process that modulates the frequency, rate or extent c SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.06 1/173</td>
    <td>0.79698703</td>
  </tr>
  <tr>
    <td>GO:0006928</td>
    <td>movement of cell or subcellular component</td>
    <td>The directed, self-propelled movement of a cell or subcell GP2</td>
    <td>7.14 1/14</td>
    <td>0.06 1/170</td>
    <td>0.79698703</td>
  </tr>
  <tr>
    <td>GO:0009889</td>
    <td>regulation of biosynthetic process</td>
    <td>Any process that modulates the frequency, rate or extent c ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.06 2/343</td>
    <td>0.79698703</td>
  </tr>
</table>
<table>
  <tr>
    <td>GO:0048518</td>
    <td>positive regulation of biological process</td>
  </tr>
  <tr>
    <td>GO:0007399</td>
    <td>nervous system development</td>
  </tr>
  <tr>
    <td>GO:0043412</td>
    <td>macromolecule modification</td>
  </tr>
  <tr>
    <td>GO:0031326</td>
    <td>regulation of cellular biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0031323</td>
    <td>regulation of cellular metabolic process</td>
  </tr>
  <tr>
    <td>GO:0051649</td>
    <td>establishment of localization in cell</td>
  </tr>
  <tr>
    <td>GO:0071704</td>
    <td>organic substance metabolic process</td>
  </tr>
  <tr>
    <td>GO:0009987</td>
    <td>cellular process</td>
  </tr>
  <tr>
    <td>GO:0051239</td>
    <td>regulation of multicellular organismal process</td>
  </tr>
  <tr>
    <td>GO:0002376</td>
    <td>immune system process</td>
  </tr>
  <tr>
    <td>GO:0031323</td>
    <td>negative regulation of cellular metabolic process</td>
  </tr>
  <tr>
    <td>GO:0048523</td>
    <td>negative regulation of cellular process</td>
  </tr>
  <tr>
    <td>GO:0009653</td>
    <td>anatomical structure morphogenesis</td>
  </tr>
  <tr>
    <td>GO:0008152</td>
    <td>metabolic process</td>
  </tr>
  <tr>
    <td>GO:0044237</td>
    <td>cellular metabolic process</td>
  </tr>
  <tr>
    <td>GO:0007166</td>
    <td>cell surface receptor signaling pathway</td>
  </tr>
  <tr>
    <td>GO:0007154</td>
    <td>cell communication</td>
  </tr>
  <tr>
    <td>GO:0010605</td>
    <td>negative regulation of macromolecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0048522</td>
    <td>positive regulation of cellular process</td>
  </tr>
  <tr>
    <td>GO:0031323</td>
    <td>positive regulation of cellular metabolic process</td>
  </tr>
  <tr>
    <td>GO:0006807</td>
    <td>nitrogen compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0016043</td>
    <td>cellular component organization</td>
  </tr>
  <tr>
    <td>GO:0043170</td>
    <td>macromolecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0080090</td>
    <td>regulation of primary metabolic process</td>
  </tr>
  <tr>
    <td>GO:0071840</td>
    <td>cellular component organization or biogenesis</td>
  </tr>
  <tr>
    <td>GO:0050789</td>
    <td>regulation of biological process</td>
  </tr>
  <tr>
    <td>GO:0065008</td>
    <td>regulation of biological quality</td>
  </tr>
  <tr>
    <td>GO:0044249</td>
    <td>cellular biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:1901576</td>
    <td>organic substance biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0009058</td>
    <td>biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0007165</td>
    <td>signal transduction</td>
  </tr>
  <tr>
    <td>GO:0065007</td>
    <td>biological regulation</td>
  </tr>
  <tr>
    <td>GO:1901362</td>
    <td>organic cyclic compound biosynthetic process</td>
  </tr>
  <tr>
    <td>GO:0023052</td>
    <td>signaling</td>
  </tr>
  <tr>
    <td>GO:0044238</td>
    <td>primary metabolic process</td>
  </tr>
  <tr>
    <td>GO:0010468</td>
    <td>regulation of gene expression</td>
  </tr>
  <tr>
    <td>GO:1901360</td>
    <td>organic cyclic compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0050794</td>
    <td>regulation of cellular process</td>
  </tr>
  <tr>
    <td>GO:0010467</td>
    <td>gene expression</td>
  </tr>
  <tr>
    <td>GO:0034641</td>
    <td>cellular nitrogen compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0060255</td>
    <td>regulation of macromolecule metabolic process</td>
  </tr>
  <tr>
    <td>GO:0006725</td>
    <td>cellular aromatic compound metabolic process</td>
  </tr>
  <tr>
    <td>GO:0046483</td>
    <td>heterocycle metabolic process</td>
  </tr>
  <tr>
    <td>GO:0008150</td>
    <td>biological_process</td>
  </tr>
</table>

<table>
  <tr>
    <td>Any process that activates or increases the frequency, rate ALPL CNTFR SH3GLE 21.43 3/14</td>
    <td>0.06 3/4951</td>
    <td>0,79698703</td>
  </tr>
  <tr>
    <td>The process whose specific outcome is the progression of MARCKS</td>
    <td>7.14 1/14</td>
    <td>0.06 1/1711</td>
    <td>0,79698703</td>
  </tr>
  <tr>
    <td>The covalent alteration of one or more monomeric units in BSPRY KRT10</td>
    <td>14.29 2/14</td>
    <td>0.06 2/3411</td>
    <td>0,79698703</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.06 2/3381</td>
    <td>0,79698703</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ERLIN2 IDH1 SH3GL</td>
    <td>21.43 3/14</td>
    <td>0.06 3/5021</td>
    <td>0,79698703</td>
  </tr>
  <tr>
    <td>Any process, occurring in a cell, that localizes a substance O NAPA</td>
    <td>7.14 1/14</td>
    <td>0.06 1/1781</td>
    <td>0,804324588</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving an organic ALPL ANXA7 BSPRY</td>
    <td>57.14 8/14</td>
    <td>0.06 8/1231</td>
    <td>0,8067419</td>
  </tr>
  <tr>
    <td>Any process that is carried out at the cellular level, but not ALPL ANXA7 BSPRY</td>
    <td>92.86 13/14</td>
    <td>0.07 13/181</td>
    <td>0,81858918</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ALPL</td>
    <td>7.14 1/14</td>
    <td>0.05 1/1941</td>
    <td>0,832200855</td>
  </tr>
  <tr>
    <td>Any process involved in the development or functioning of GP2</td>
    <td>7.14 1/14</td>
    <td>0.05 1/2041</td>
    <td>0,847565399</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents, or reduces the frequency C ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.05 1/2031</td>
    <td>0,847565399</td>
  </tr>
  <tr>
    <td>Any process that stops, prevents, or reduces the frequency CNTFR ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.05 2/3851</td>
    <td>0,848931299</td>
  </tr>
  <tr>
    <td>The process in which anatomical structures are generated ALPL</td>
    <td>7.14 1/14</td>
    <td>0.05 1/2101</td>
    <td>0,854299974</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways, including anabolism ALPL ANXA7 BSPRY</td>
    <td>57.14 8/14</td>
    <td>0.06 8/1291</td>
    <td>0,864376958</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways by which individual C ALPL ANXA7 BSPRY</td>
    <td>50.00 7/14</td>
    <td>0.06 7/1151</td>
    <td>0,864687819</td>
  </tr>
  <tr>
    <td>A series of molecular signals initiated by activation of a rec CNTFR</td>
    <td>7.14 1/14</td>
    <td>0.04 1/2251</td>
    <td>0,872935767</td>
  </tr>
  <tr>
    <td>Any process that mediates interactions between a cell and CNTFR ERLIN2 SH3C</td>
    <td>21.43 3/14</td>
    <td>0.05 3/6061</td>
    <td>0,903627165</td>
  </tr>
  <tr>
    <td>Any process that decreases the frequency, rate or extent O ANXA7</td>
    <td>7.14 1/14</td>
    <td>0.04 1/2561</td>
    <td>0,910119162</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate CNTFR SH3GLB1</td>
    <td>14.29 2/14</td>
    <td>0.04 2/4481</td>
    <td>0,910119162</td>
  </tr>
  <tr>
    <td>Any process that activates or increases the frequency, rate SH3GLB1</td>
    <td>7.14 1/14</td>
    <td>0.04 1/2631</td>
    <td>0,914830252</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving organic or C ALPL BSPRY CD5L EF 42.86 6/14</td>
    <td>0.05 6/1091</td>
    <td>0,919988415</td>
  </tr>
  <tr>
    <td>A process that results in the assembly, arrangement of con KRT10 MARCKS SH3 21.43 3/14</td>
    <td>0.05 3/6351</td>
    <td>0,919988415</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving macromolecule ANXA7 BSPRY CD5L</td>
    <td>42.86 6/14</td>
    <td>0.05 6/1091</td>
    <td>0,919988415</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.04 2/4851</td>
    <td>0,930689335</td>
  </tr>
  <tr>
    <td>A process that results in the biosynthesis of constituent m KRT10 MARCKS SH3 21.43 3/14</td>
    <td>0.05 3/6561</td>
    <td>0,930689335</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ALPL ANXA7 CNTFR</td>
    <td>42.86 6/14</td>
    <td>0.05 6/1111</td>
    <td>0,931829975</td>
  </tr>
  <tr>
    <td>Any process that modulates a qualitative or quantitative tr ALPL</td>
    <td>7.14 1/14</td>
    <td>0.03 1/2951</td>
    <td>0,932184262</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.04 2/5091</td>
    <td>0,941637763</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.04 2/5161</td>
    <td>0,944150782</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2 IDH1</td>
    <td>14.29 2/14</td>
    <td>0.04 2/5231</td>
    <td>0,94611299</td>
  </tr>
  <tr>
    <td>The cellular process in which a signal is conveyed to trigei CNTFR ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.04 2/5641</td>
    <td>0,96237207</td>
  </tr>
  <tr>
    <td>Any process that modulates a measurable attribute of any ALPL ANXA7 CNTFR</td>
    <td>42.86 6/14</td>
    <td>0.05 6/1191</td>
    <td>0,96237207</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways resulting in the form ERLIN2</td>
    <td>7.14 1/14</td>
    <td>0.03 1/3551</td>
    <td>0,96237207</td>
  </tr>
  <tr>
    <td>The entirety of a process in which information is transmitt CNTFR ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.03 2/6021</td>
    <td>0,97662684</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving those com BSPRY CD5L ERLIN2</td>
    <td>35.71 5/14</td>
    <td>0.04 5/1141</td>
    <td>0,988590329</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ANXA7</td>
    <td>7.14 1/14</td>
    <td>0.02 1/4341</td>
    <td>0,988590329</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving organic cyc ALPL ERLIN2</td>
    <td>14.29 2/14</td>
    <td>0.03 2/7061</td>
    <td>0,995002214</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent CNTFR ERLIN2 IDH1</td>
    <td>28.57 4/14</td>
    <td>0.04 4/1031</td>
    <td>0,995002214</td>
  </tr>
  <tr>
    <td>The process in which a gene's sequence is converted into a ANXA7 CD5L</td>
    <td>14.29 2/14</td>
    <td>0.03 2/7481</td>
    <td>0,996675729</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving various org ALPL IDH1</td>
    <td>14.29 2/14</td>
    <td>0.03 2/7591</td>
    <td>0,996675729</td>
  </tr>
  <tr>
    <td>Any process that modulates the frequency, rate or extent C ANXA7</td>
    <td>7.14 1/14</td>
    <td>0.02 1/5551</td>
    <td>0,996675729</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving aromatic c1 ALPL</td>
    <td>7.14 1/14</td>
    <td>0.01 1/6891</td>
    <td>0,99970648</td>
  </tr>
  <tr>
    <td>The chemical reactions and pathways involving heterocyc1 ALPL</td>
    <td>7.14 1/14</td>
    <td>0.01 1/6821</td>
    <td>0,99970648</td>
  </tr>
  <tr>
    <td>A biological process represents a specific objective that the ALPL ANXA7 BSPRY</td>
    <td>100.00 14/14</td>
    <td>0.07 14/201</td>
    <td>1</td>
  </tr>
</table>
GO:0006869 lipid transport
GO:0033598 mammary gland epithelial cell proliferation
GO:0014910 regulation of smooth muscle cell migration
GO:0033146 regulation of intracellular estrogen receptor signaling pathway
GO:0060603 mammary gland duct morphogenesis
GO:0046741 phosphatidylglycerol metabolic process
GO:0030224 monocyte differentiation
GO:0008053 mitochondrial fusion
GO:0051128 regulation of cellular component organization
GO:0048662 negative regulation of smooth muscle cell proliferation
GO:0006644 phospholipid metabolic process
GO:0030851 granulocyte differentiation
GO:0045806 negative regulation of endocytosis
GO:0043001 Golgi to plasma membrane protein transport
GO:0046486 glycerolipid metabolic process
GO:0033144 negative regulation of intracellular steroid hormone receptor signaling pathway
GO:0008542 visual learning
GO:0007346 regulation of mitotic cell cycle
GO:0010518 positive regulation of phospholipase activity
GO:0071827 plasma lipoprotein particle organization
GO:0014909 smooth muscle cell migration
GO:0000280 nuclear division
GO:0007632 visual behavior
GO:0043410 positive regulation of MAPK cascade
GO:0010823 negative regulation of mitochondrion organization
GO:0071825 protein-lipid complex subunit organization
GO:0002090 regulation of receptor internalization
GO:0002066 column/cuboidal epithelial cell development
GO:1902808 positive regulation of cell cycle G1/S phase transition
GO:0010517 regulation of phospholipase activity
GO:0061028 establishment of endothelial barrier
GO:0060443 mammary gland morphogenesis
GO:0016126 steral biosynthetic process
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
GO:1901568 fatty acid derivative metabolic process
GO:0030520 intracellular estrogen receptor signaling pathway
GO:0002639 positive regulation of immunoglobulin production
GO:0060688 regulation of morphogenesis of a branching structure
GO:0007102 organic substance transport
GO:0048285 organelle fission
GO:0072583 clathrin-dependent endocytosis
GO:0060193 positive regulation of lipase activity
GO:0002067 glandular epithelial cell differentiation
GO:0006893 Golgi to plasma membrane transport
GO:0014812 muscle cell migration
GO:0007005 mitochondrion organization
GO:1903078 positive regulation of protein localization to plasma membrane
GO:0061951 establishment of protein localization to plasma membrane
GO:0097006 regulation of plasma lipoprotein particle levels
GO:1905330 regulation of morphogenesis of an epithelium
GO:0042127 regulation of cell population proliferation
GO:0046470 phosphatidylcholine metabolic process
GO:0048856 anatomical structure development
GO:0048278 vesicle docking
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0008036 associative learning
GO:0007062 sister chromatid cohesion
GO:0032787 monocarboxylic acid metabolic process
GO:0008285 negative regulation of cell population proliferation
GO:0060191 regulation of lipase activity
GO:0001885 endothelial cell development
GO:1904377 positive regulation of protein localization to cell periphery
GO:0098586 cell response to virus
GO:0002637 regulation of immunoglobulin production
GO:0033143 regulation of intracellular steroid hormone receptor signaling pathway
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:0046889 positive regulation of lipid biosynthetic process
GO:0015909 long-chain fatty acid transport
GO:0006996 organelle organization
GO:0061180 mammary gland epithelium development
GO:0051129 negative regulation of cellular component organization
GO:0061912 selective autophagy
GO:0010564 regulation of cell cycle process
GO:0048259 regulation of receptor-mediated endocytosis
GO:0043408 regulation of MAPK cascade
GO:0000422 autophagy of mitochondrion
go:0071626 mitochondrion disassembly
GO:1901992 positive regulation of mitotic cell cycle phase transition
GO:0001676 long-chain fatty acid metabolic process
GO:0051668 localization within membrane
GO:0032456 endocytic recycling
GO:0140056 organelle localization by membrane tethering
GO:0019915 lipid storage
GO:0046907 intracellular transport
GO:0051341 regulation of oxidoreductase activity
GO:0002065 column/cuboidal epithelial cell differentiation
GO:0032502 developmental process
GO:0035383 thioester metabolic process
GO:0015908 fatty acid transport
GO:0006637 acyl-CoA metabolic process
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048659 smooth muscle cell proliferation
GO:0022406 membrane docking
GO:1905477 positive regulation of protein localization to membrane
GO:0006892 post-Golgi vesicle-mediated transport
GO:1903047 mitotic cell cycle process
GO:0000165 MAPK cascade
GO:1901222 regulation of NIK/NF-kappaB signaling
GO:0008283 cell population proliferation
GO:0032880 regulation of protein localization
GO:0045446 endothelial cell differentiation
GO:0002377 immunoglobulin production
GO:0032368 regulation of lipid transport
GO:0048731 system development
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0034032 purine nucleoside bisphosphate metabolic process
GO:0007088 regulation of mitotic nuclear division
GO:1903076 regulation of protein localization to plasma membrane
GO:0033865 nucleoside bisphosphate metabolic process

The directed movement of lipids into, out of or within a cell, ACSL3 SURF4
8.33 1/12 0.60 2/332 0.0906447
The multiplication or reproduction of mammary gland epithelium PHB2
8.33 1/12 3.70 1/27 0.0906447
Any process that modulates the frequency, rate or extent of: NDRG4
8.33 1/12 3.85 1/26 0.0906447
Any process that modulates the frequency, rate or extent of: PHB2
8.33 1/12 3.85 1/26 0.0906447
The process in which anatomical structures of the mammary PHB2
8.33 1/12 3.70 1/27 0.0906447
The chemical reactions and pathways involving phosphatidylyl PHB2
8.33 1/12 3.70 1/27 0.0906447
The process in which a relatively unspecialized myeloid preci FASN
8.33 1/12 3.85 1/26 0.0906447
Merging of two or more mitochondria within a cell to form a VAT1
33.33 4/12 0.23 4/1732 0.0906447
Any process that stops, prevents or reduces the rate or extent NDRG4
8.33 1/12 3.57 1/28 0.0914053
The chemical reactions and pathways involving phospholipid: ACSL3 PHB2
16.67 2/12 0.59 2/338 0.0914053
The process in which a myeloid precursor cell acquires the sc FASN
8.33 1/12 3.57 1/28 0.0914053
Any process that stops, prevents, or reduces the frequency, r ANKRD13A
8.33 1/12 3.45 1/29 0.0928188
The directed movement of proteins from the Golgi to the pla ACSL3
8.33 1/12 3.45 1/29 0.0928188
The chemical reactions and pathways involving glycerolipids, ACSL3 PHB2
16.67 2/12 0.58 2/347 0.0936966
Any process that stops, prevents, or reduces the frequency, r ANKRD13A CUL9 SURF4 VAT1
8.33 1/12 3.33 1/30 0.0944323
8.33 1/12 3.23 1/31 0.0944809
Any process in an organism in which a change in behavior of NDRG4
8.33 1/12 0.57 2/353 0.0944809
Any process that modulates the rate or extent of progress th CUL9 PHB2
8.33 1/12 3.23 1/31 0.0944809
A protein-lipid complex subunit organization process that res ACSL3
8.33 1/12 3.23 1/31 0.0944809
The orderly movement of a smooth muscle cell from one site to NDRG4
8.33 1/12 3.12 1/32 0.0967403
The division of a cell nucleus into two nuclei, with DNA and o CUL9 PHB2
8.33 1/12 0.54 2/372 0.0988684
The behavior of an organism in response to a visual stimulus, NDRG4
8.33 1/12 0.54 2/373 0.0988684
Any process that activates or increases the frequency, rate or NDRG4 PHB2
8.33 1/12 2.94 1/34 0.0988684
Any process in which macromolecules aggregate, disaggrega: ACSL3
8.33 1/12 2.94 1/34 0.0988684
Any process that modulates the frequency, rate or extent of ANKRD13A
8.33 1/12 2.78 1/36 0.1015722
The process whose specific outcome is the progression of a c FASN
8.33 1/12 2.78 1/36 0.1015722
Any signalling pathway that activates or increases the activity, PHB2
8.33 1/12 2.78 1/36 0.1015722
Any process that modulates the frequency, rate or extent of: PHB2
8.33 1/12 2.56 1/39 0.1046019
The establishment of a barrier between endothelial cell layer FASN
8.33 1/12 2.56 1/39 0.1046019
The process in which anatomical structures of the mammary PHB2
8.33 1/12 2.56 1/39 0.1046019
The chemical reactions and pathways resulting in the format: SOLQ
8.33 1/12 2.56 1/39 0.1046019
Any series of molecular signals generated as a consequence c PHB2
8.33 1/12 2.63 1/38 0.1046019
The chemical reactions and pathways involving fatty acid der ACSL3
8.33 1/12 2.63 1/38 0.1046019
Any process that activates or increases the frequency, rate, o PHB2
8.33 1/12 2.63 1/38 0.1046019
Any process that modulates the rate, frequency, or extent of PHB2
8.33 1/12 2.50 1/40 0.106515
The directed movement of organic substances into, out of or ACSL3 AP281 PHB2 SURF4
16.67 2/12 0.20 4/1968 0.1066871
The creation of two or more organelles by division of one org CUL9 PHB2
16.67 2/12 0.48 2/414 0.1075817
An endocytosis process that begins when material is taken up: AP281
8.33 1/12 2.44 1/41 0.1075817
Any process that increases the frequency, rate or extent of: IIP PHB2
8.33 1/12 2.33 1/43 0.1113885
The process in which a relatively unspecialized cell acquires s FASN
8.33 1/12 2.27 1/44 0.1123881
The directed movement of substances from the Golgi to the ACSL3
8.33 1/12 2.27 1/44 0.1123881
The orderly movement of a muscle cell from one site to anot NDRG4
8.33 1/12 2.22 1/45 0.1141551
A process that is carried out at the cellular level which result: PHB2 VAT1
16.67 2/12 0.45 2/444 0.1170456
Any process that activates or increases the frequency, rate or PHB2
8.33 1/12 2.08 1/48 0.1170456
The directed movement of a protein to a specific location in ACSL3
8.33 1/12 2.13 1/47 0.1170456
Any process involved in the maintenance of internal levels of ACSL3
8.33 1/12 2.08 1/48 0.1170456
Any process that modulates the frequency, rate or extent of: PHB2
8.33 1/12 2.08 1/48 0.1170456
Any process that modulates the frequency, rate or extent of: NDRG4 PHB2 SOLQ
8.33 1/12 2.04 1/49 0.1179583
The chemical reactions and pathways involving phosphatidylyl ACSL3
The biological process whose specific outcome is the progres CMTM8 FASN NDRG4 PHB2 VAT1
8.33 1/12 2.00 1/50 0.1188472
The series of molecular signals generated as a consequence c NDRG4
8.33 1/12 2.00 1/50 0.1188472
Learning by associating a stimulus (the cause) with a particular NDRG4
8.33 1/12 1.96 1/51 0.1197131
The cell cycle process in which the sister chromatids of a repl PHB2
8.33 1/12 1.96 1/51 0.1197131
The chemical reactions and pathways involving monocarboxyl ACSL3 FASN
16.67 2/12 0.43 2/470 0.120659
16.67 2/12 0.43 2/469 0.120659
Any process that stops, prevents or reduces the rate or exten NDRG4 PHB2
8.33 1/12 1.92 1/52 0.120659
The progression of an endothelial cell over time, from its for: FASN
8.33 1/12 1.89 1/53 0.1213794
Any process that activates or increases the frequency, rate o ACSL3
8.33 1/12 1.85 1/54 0.1229043
Any process that results in a change in state or activity of a ci PHB2
8.33 1/12 1.79 1/56 0.125165
8.33 1/12 1.79 1/56 0.125165
Any process that modulates the frequency, rate, or extent of PHB2
8.33 1/12 1.75 1/57 0.1266291
Any process that activates or increases the frequency, rate or ACSL3
8.33 1/12 1.72 1/58 0.1280752
The directed movement of long-chain fatty acids into, out of ACSL3
41.67 5/12 0.15 5/3300 0.130146
The process that is carried out at the cellular level which result: CUL9 PHB2 SOLQ SURF4 VAT1
8.33 1/12 1.67 1/60 0.130146
Any process that stops, prevents, or reduces the frequency, r ANKRD13A VAT1
8.33 1/12 1.64 1/61 0.1308302
Any process that modulates a cellular process that is involved CUL9 PHB2
8.33 1/12 0.38 2/520 0.1340659
8.33 1/12 1.59 1/63 0.1340659
16.67 2/12 0.38 2/524 0.1352115
The autophagic process in which mitochondria are delivered PHB2
8.33 1/12 1.52 1/66 0.1375199
The disaggregation of a mitochondrion into its constituent cc FASN
8.33 1/12 1.52 1/66 0.1375199
Any process that activates or increases the frequency, rate o PHB2
The chemical reactions and pathways involving long-chain fai ACSL3
Any process in which a substance or cellular entity, such as a ACSL3 NDRG4
The directed movement of membrane-bounded vesicles from NDRG4
The process by which an organelle membrane interacts with NDRG4
8.33 1/12 1.49 1/67 0.1380196
8.33 1/12 1.47 1/68 0.1380196
16.67 2/12 0.37 2/541 0.1380196
16.67 2/12 0.47 1/68 0.1380196
The accumulation and maintenance in cells or tissues of lipid SOLQ
25.00 3/12 0.22 3/1335 0.1396249
Any process that modulates the frequency, rate or extent of ACSL3
8.33 1/12 1.43 1/70 0.1396249
The process in which a relatively unspecialized cell acquires s FASN
8.33 1/12 1.39 1/72 0.1398364
A biological process whose specific outcome is the progress CMTM8 FASN NDRG4 PHB2 VAT1
8.33 1/12 1.39 1/72 0.1398364
The chemical reactions and pathways involving a thioester, a ACSL3
8.33 1/12 1.39 1/72 0.1398364
The directed movement of fatty acids into, out of or within a ACSL3
8.33 1/12 1.39 1/72 0.1398364
The chemical reactions and pathways involving acyl-CoA, any ACSL3
8.33 1/12 1.41 1/71 0.1398364
Any process that modulates the frequency, rate or extent of: NDRG4
The multiplication or reproduction of smooth muscle cells, re NDRG4
8.33 1/12 1.37 1/73 0.1403721
The initial attachment of a membrane or protein to a target NDRG4
Any process that activates or increases the frequency, rate or ACSL3
8.33 1/12 1.32 1/76 0.1438528
The directed movement of substances from the Golgi to othe ACSL3
8.33 1/12 1.32 1/76 0.1438528
A process that is part of the mitotic cell cycle. CUL9 PHB2
An intracellular protein kinase cascade containing at least a NDRG4 PHB2
8.33 1/12 0.34 2/584 0.1476475
8.33 1/12 0.34 2/591 0.1479802
Any process that modulates the frequency, rate or extent of: PHB2
8.33 1/12 1.23 1/81 0.1479802
The multiplication or reproduction of cells, resulting in the e NDRG4 PHB2 SOLQ
25.00 3/12 0.21 3/1409 0.1479802
Any process that modulates the frequency, rate or extent of: ACSL3 ANKRD13A
16.67 2/12 0.34 2/594 0.1479802
The process in which a mesodermal, bone marrow or neural FASN
8.33 1/12 1.23 1/81 0.1479802
The appearance of immunoglobulin due to biosynthesis or se PHB2
8.33 1/12 1.23 1/81 0.1479802
Any process that modulates the frequency, rate or extent of: SURF4
41.67 5/12 0.14 5/3612 0.149056
A series of molecular signals generated as a consequence of an ACSL3 CMTM8 FASN NDRG4 PHB2
8.33 1/12 1.19 1/84 0.149056
The chemical reactions and pathways involving a purine nucl- ACSL3
8.33 1/12 1.16 1/86 0.149056
Any process that modulates the frequency, rate or extent of: CUL9
8.33 1/12 1.18 1/85 0.149056
Any process that modulates the frequency, rate or extent of: ACSL3
8.33 1/12 1.16 1/86 0.149056
The chemical reactions and pathways involving a nucleoside ACSL3